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204 results on '"Adler, Thure"'

2. Physiological relevance of the neuronal isoform of inositol-1,4,5-trisphosphate 3-kinases in mice

Author

Blechner, Christine, Becker, Lore, Fuchs, Helmut, Rathkolb, Birgit, Prehn, Cornelia, Adler, Thure, Calzada-Wack, Julia, Garrett, Lillian, Gailus-Durner, Valerie, Morellini, Fabio, Conrad, Susanne, Hölter, Sabine M., Wolf, Eckhard, Klopstock, Thomas, Adamski, Jerzy, Busch, Dirk, de Angelis, Martin Hrabe, Schmeisser, Michael J., and Windhorst, Sabine

Published
2020
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3. A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene

Author

Jensen, Lars R., Garrett, Lillian, Hölter, Sabine M., Rathkolb, Birgit, Rácz, Ildikó, Adler, Thure, Prehn, Cornelia, Hans, Wolfgang, Rozman, Jan, Becker, Lore, Aguilar-Pimentel, Juan Antonio, Puk, Oliver, Moreth, Kristin, Dopatka, Monika, Walther, Diego J., von Bohlen und Halbach, Viola, Rath, Matthias, Delatycki, Martin, Bert, Bettina, Fink, Heidrun, Blümlein, Katharina, Ralser, Markus, Van Dijck, Anke, Kooy, Frank, Stark, Zornitza, Müller, Sabine, Scherthan, Harry, Gecz, Jozef, Wurst, Wolfgang, Wolf, Eckhard, Zimmer, Andreas, Klingenspor, Martin, Graw, Jochen, Klopstock, Thomas, Busch, Dirk, Adamski, Jerzy, Fuchs, Helmut, Gailus-Durner, Valérie, de Angelis, Martin Hrabě, von Bohlen und Halbach, Oliver, Ropers, Hans-Hilger, and Kuss, Andreas W.

Published
2019
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4. Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice

Author

Xie, Kan, Ryan, Devon P., Pearson, Brandon L., Henzel, Kristin S., Neff, Frauke, Vidal, Ramon O., Hennion, Magali, Lehmann, Isabelle, Schleif, Melvin, Schröder, Susanne, Adler, Thure, Rathkolb, Birgit, Rozman, Jan, Schütz, Anna-Lena, Prehn, Cornelia, Mickael, Michel E., Weiergräber, Marco, Adamski, Jerzy, Busch, Dirk H., Ehninger, Gerhard, Matynia, Anna, Jackson, Walker S., Wolf, Eckhard, Fuchs, Helmut, Gailus-Durner, Valerie, Bonn, Stefan, de Angelis, Martin Hrabě, and Ehninger, Dan

Published
2018

5. Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke

Author

Casas, Ana I., Kleikers, Pamela W.M., Geuss, Eva, Langhauser, Friederike, Adler, Thure, Busch, Dirk H., Gailus-Durner, Valerie, de Angelis, Martin Hrabe, Egea, Javier, Lopez, Manuela G., Kleinschnitz, Christoph, and Schmidt, Harald H.H.W.

Subjects
Blood-brain barrier -- Research, Disabilities -- Risk factors, Laboratory rats -- Models -- Usage, Stroke -- Patient outcomes -- Care and treatment -- Complications and side effects, Enzymes, Oxidases, Ischemia, B cells, Health care industry
Abstract

Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal of the occlusion being the only therapeutic option. Reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain barrier. Its mechanism, however, is unknown. Here, we identified type 5 NADPH oxidase (NOX5), a calcium-activated, ROS-forming enzyme, as the missing link. Using a humanized knockin (KI) mouse model and in vitro organotypic cultures, we found that reoxygenation or calcium overload increased brain ROS levels in a NOX5-dependent manner. In vivo, postischemic ROS formation, infarct volume, and functional outcomes were worsened in NOX5-KI mice. Of clinical and therapeutic relevance, in a human blood-barrier model, pharmacological NOX inhibition also prevented acute reoxygenation-induced leakage. Our data support further evaluation of poststroke recanalization in the presence of NOX inhibition for limiting stroke-induced damage., Introduction Ischemic stroke represents one of the most frequent causes of death and leading causes of disability worldwide (1). Thrombolytic or mechanical removal of the occlusion is the only therapeutic [...]

Published
2019
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6. The Role of Fibroblast Growth Factor-Binding Protein 1 in Skin Carcinogenesis and Inflammation

Author

Becker, Lore, Vernaleken, Alexandra, Klopstock, Thomas, Adler, Thure, Treise, Irina, Horsch, Marion, Moreth, Kristin, Brommage, Robert, Hans, Wolfgang, Östereicher, Manuela, Steinkamp, Ralph, Lengger, Christoph, Maier, Holger, Stoeger, Claudia, Leuchtenberger, Stefanie, Busch, Dirk H., Beckers, Johannes, Bekeredjian, Raffi, Garrett, Lillian, Hölter, Sabine M., Zimprich, Annemarie, Amarie, Oana, Wurst, Wolfgang, Graw, Jochen, Rozman, Jan, Calzada-Wack, Julia, da Silva-Buttkus, Patricia, Neff, Frauke, Klingenspor, Martin, Racz, Ildiko, Zimmer, Andreas, Rathkolb, Birgit, Wolf, Eckhard, Schmidt, Marcel Oliver, Garman, Khalid Ammar, Lee, Yong Gu, Zuo, Chong, Beck, Patrick James, Tan, Mingjun, Aguilar-Pimentel, Juan Antonio, Ollert, Markus, Schmidt-Weber, Carsten, Fuchs, Helmut, Gailus-Durner, Valerie, Hrabe de Angelis, Martin, Tassi, Elena, Riegel, Anna Tate, and Wellstein, Anton

Published
2018
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9. Mouse Genetics and Metabolic Mouse Phenotyping

Author

Fuchs, Helmut, Neschen, Susanne, Rozman, Jan, Rathkolb, Birgit, Wagner, Sibylle, Adler, Thure, Afonso, Luciana, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Bohla, Alexander, Calzada-Wack, Julia, Cohrs, Christian, Frankó, András, Garrett, Lillian, Glasl, Lisa, Götz, Alexander, Hagn, Michael, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Kahle, Melanie, Kistler, Martin, Klein-Rodewald, Tanja, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Marschall, Susan, Micklich, Kateryna, Möller, Gabriele, Naton, Beatrix, Neff, Frauke, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Räß, Michael, Scheerer, Markus, Schiller, Evelyn, Schöfer, Felix, Schrewe, Anja, Steinkamp, Ralph, Stöger, Claudia, Treise, Irina, Willershäuser, Monja, Wolff-Muscate, Annemarie, Zeh, Ramona, Adamski, Jerzy, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H., Favor, Jack, Graw, Jochen, Katus, Hugo, Klopstock, Thomas, Ollert, Markus, Schulz, Holger, Stöger, Tobias, Wurst, Wolfgang, Yildirim, Ali Önder, Zimmer, Andreas, Wolf, Eckhard, Klingenspor, Martin, Gailus-Durner, Valérie, de Angelis, Martin Hrabě, and Suhre, Karsten, editor

Published
2012
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10. The German Mouse Clinic – Running an Open Access Platform

Author

Gailus-Durner, Valérie, Naton, Beatrix, Adler, Thure, Afonso, Luciana, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Calzada-Wack, Julia, Cohrs, Christian, da Silva-Buttkus, Patricia, Hans, Wolfgang, Horsch, Marion, Kahle, Melanie, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Micklich, Kateryna, Möller, Gabriele, Neff, Frauke, Neschen, Susanne, Prehn, Cornelia, Rathkolb, Birgit, Rozman, Jan, Schiller, Evelyn, Schrewe, Anja, Scheerer, Markus, Schöfer, Felix, Steinkamp, Ralph, Stöger, Claudia, Thiele, Frank, Tost, Monica, Treise, Irina, Willershäuser, Monja, Zeh, Ramona, Adamski, Jerzy, Bekeredjian, Raffi, Beckers, Johannes, Esposito, Irene, Höfler, Heinz, Katus, Hugo, Klingenspor, Martin, Klopstock, Thomas, Ollert, Markus, Wolf, Eckhard, Busch, Dirk H., Fuchs, Helmut, Hrabě de Angelis, Martin, Brakebusch, Cord, editor, and Pihlajaniemi, Taina, editor

Published
2011
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11. An ENU Mutagenesis-Derived Mouse Model with a Dominant Jak1 Mutation Resembling Phenotypes of Systemic Autoimmune Disease

Author

Sabrautzki, Sibylle, Janas, Eva, Lorenz-Depiereux, Bettina, Calzada-Wack, Julia, Aguilar-Pimentel, Juan A., Rathkolb, Birgit, Adler, Thure, Cohrs, Christian, Hans, Wolfgang, Diener, Susanne, Fuchs, Helmut, Gailus-Durner, Valerie, Busch, Dirk H., Höfler, Heinz, Ollert, Markus, Strom, Tim M., Wolf, Eckhard, Neff, Frauke, and Hrabě de Angelis, Martin

Published
2013
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12. High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner

Author

Kugler, Jamie E., Horsch, Marion, Huang, Di, Furusawa, Takashi, Rochman, Mark, Garrett, Lillian, Becker, Lore, Bohla, Alexander, Hölter, Sabine M., Prehn, Cornelia, Rathkolb, Birgit, Racz, Ildikó, Aguilar-Pimentel, Juan Antonio, Adler, Thure, Adamski, Jerzy, Beckers, Johannes, Busch, Dirk H., Eickelberg, Oliver, Klopstock, Thomas, Ollert, Markus, Stöger, Tobias, Wolf, Eckhard, Wurst, Wolfgang, Yildirim, Ali Önder, Zimmer, Andreas, Gailus-Durner, Valérie, Fuchs, Helmut, Hrabě de Angelis, Martin, Garfinkel, Benny, Orly, Joseph, Ovcharenko, Ivan, and Bustin, Michael

Published
2013
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13. SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities

Author

Ju, Limei, Wing, Jonathan, Taylor, Elaine, Brandt, Renata, Slijepcevic, Predrag, Horsch, Marion, Rathkolb, Birgit, Rácz, Ildikó, Becker, Lore, Hans, Wolfgang, Adler, Thure, Beckers, Johannes, Rozman, Jan, Klingenspor, Martin, Wolf, Eckhard, Zimmer, Andreas, Klopstock, Thomas, Busch, Dirk H., Gailus-Durner, Valérie, Fuchs, Helmut, Angelis, Martin Hrabě de, van der Horst, Gilbertus, and Lehmann, Alan R.

Published
2013
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14. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics

Author

Hrabě de Angelis, Martin, Nicholson, George, Selloum, Mohammed, White, Jacqueline K, Morgan, Hugh, Ramirez-Solis, Ramiro, Sorg, Tania, Wells, Sara, Fuchs, Helmut, Fray, Martin, Adams, David J, Adams, Niels C, Adler, Thure, Aguilar-Pimentel, Antonio, Ali-Hadji, Dalila, Amann, Gregory, André, Philippe, Atkins, Sarah, Auburtin, Aurelie, Ayadi, Abdel, Becker, Julien, Becker, Lore, Bedu, Elodie, Bekeredjian, Raffi, Birling, Marie-Christine, Blake, Andrew, Bottomley, Joanna, Bowl, Michael R, Brault, Véronique, Busch, Dirk H, Bussell, James N, Calzada-Wack, Julia, Cater, Heather, Champy, Marie-France, Charles, Philippe, Chevalier, Claire, Chiani, Francesco, Codner, Gemma F, Combe, Roy, Cox, Roger, Dalloneau, Emilie, Dierich, André, Di Fenza, Armida, Doe, Brendan, Duchon, Arnaud, Eickelberg, Oliver, Esapa, Chris T, Fertak, Lahcen El, Feigel, Tanja, Emelyanova, Irina, Estabel, Jeanne, Favor, Jack, Flenniken, Ann, Gambadoro, Alessia, Garrett, Lilian, Gates, Hilary, Gerdin, Anna-Karin, Gkoutos, George, Greenaway, Simon, Glasl, Lisa, Goetz, Patrice, Da Cruz, Isabelle Goncalves, Götz, Alexander, Graw, Jochen, Guimond, Alain, Hans, Wolfgang, Hicks, Geoff, Hölter, Sabine M, Höfler, Heinz, Hancock, John M, Hoehndorf, Robert, Hough, Tertius, Houghton, Richard, Hurt, Anja, Ivandic, Boris, Jacobs, Hughes, Jacquot, Sylvie, Jones, Nora, Karp, Natasha A, Katus, Hugo A, Kitchen, Sharon, Klein-Rodewald, Tanja, Klingenspor, Martin, Klopstock, Thomas, Lalanne, Valerie, Leblanc, Sophie, Lengger, Christoph, le Marchand, Elise, Ludwig, Tonia, Lux, Aline, McKerlie, Colin, Maier, Holger, Mandel, Jean-Louis, Marschall, Susan, Mark, Manuel, Melvin, David G, Meziane, Hamid, Micklich, Kateryna, Mittelhauser, Christophe, Monassier, Laurent, Moulaert, David, Muller, Stéphanie, Naton, Beatrix, Neff, Frauke, Nolan, Patrick M, Nutter, Lauryl M J, Ollert, Markus, Pavlovic, Guillaume, Pellegata, Natalia S, Peter, Emilie, Petit-Demoulière, Benoit, Pickard, Amanda, Podrini, Christine, Potter, Paul, Pouilly, Laurent, Puk, Oliver, Richardson, David, Rousseau, Stephane, Quintanilla-Fend, Leticia, Quwailid, Mohamed M, Racz, Ildiko, Rathkolb, Birgit, Riet, Fabrice, Rossant, Janet, Roux, Michel, Rozman, Jan, Ryder, Edward, Salisbury, Jennifer, Santos, Luis, Schäble, Karl-Heinz, Schiller, Evelyn, Schrewe, Anja, Schulz, Holger, Steinkamp, Ralf, Simon, Michelle, Stewart, Michelle, Stöger, Claudia, Stöger, Tobias, Sun, Minxuan, Sunter, David, Teboul, Lydia, Tilly, Isabelle, Tocchini-Valentini, Glauco P, Tost, Monica, Treise, Irina, Vasseur, Laurent, Velot, Emilie, Vogt-Weisenhorn, Daniela, Wagner, Christelle, Walling, Alison, Wattenhofer-Donze, Marie, Weber, Bruno, Wendling, Olivia, Westerberg, Henrik, Willershäuser, Monja, Wolf, Eckhard, Wolter, Anne, Wood, Joe, Wurst, Wolfgang, Yildirim, Ali Önder, Zeh, Ramona, Zimmer, Andreas, Zimprich, Annemarie, Holmes, Chris, Steel, Karen P, Herault, Yann, Gailus-Durner, Valérie, Mallon, Ann-Marie, and Brown, Steve D M

Published
2015
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15. Requirement of the RNA-editing Enzyme ADAR2 for Normal Physiology in Mice

Author

Horsch, Marion, Seeburg, Peter H., Adler, Thure, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Calzada-Wack, Julia, Garrett, Lilian, Götz, Alexander, Hans, Wolfgang, Higuchi, Miyoko, Hölter, Sabine M., Naton, Beatrix, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Rathkolb, Birgit, Rozman, Jan, Schrewe, Anja, Adamski, Jerzy, Busch, Dirk H., Esposito, Irene, Graw, Jochen, Ivandic, Boris, Klingenspor, Martin, Klopstock, Thomas, Mempel, Martin, Ollert, Markus, Schulz, Holger, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, Gailus-Durner, Valérie, Fuchs, Helmut, de Angelis, Martin Hrabě, and Beckers, Johannes

Published
2011
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16. Mouse phenotyping

Author

Fuchs, Helmut, Gailus-Durner, Valérie, Adler, Thure, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Calzada-Wack, Julia, Da Silva-Buttkus, Patricia, Neff, Frauke, Götz, Alexander, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Kastenmüller, Gabi, Kemter, Elisabeth, Lengger, Christoph, Maier, Holger, Matloka, Mikolaj, Möller, Gabriele, Naton, Beatrix, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Rathkolb, Birgit, Römisch-Margl, Werner, Rozman, Jan, Wang-Sattler, Rui, Schrewe, Anja, Stöger, Claudia, Tost, Monica, Adamski, Jerzy, Aigner, Bernhard, Beckers, Johannes, Behrendt, Heidrun, Busch, Dirk H., Esposito, Irene, Graw, Jochen, Illig, Thomas, Ivandic, Boris, Klingenspor, Martin, Klopstock, Thomas, Kremmer, Elisabeth, Mempel, Martin, Neschen, Susanne, Ollert, Markus, Schulz, Holger, Suhre, Karsten, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, and Hrabě de Angelis, Martin

Published
2011
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17. Immune modulation by Fas ligand reverse signaling: lymphocyte proliferation is attenuated by the intracellular Fas ligand domain

Author

Lückerath, Katharina, Kirkin, Vladimir, Melzer, Inga Maria, Thalheimer, Frederic B., Siele, Dagmar, Milani, Wiebke, Adler, Thure, Aguilar-Pimentel, Antonio, Horsch, Marion, Michel, Geert, Beckers, Johannes, Busch, Dirk H., Ollert, Markus, Gailus-Durner, Valerie, Fuchs, Helmut, Hrabĕ de Angelis, Martin, Staal, Frank J.T., Rajalingam, Krishnaraj, Hueber, Anne-Odile, Strobl, Lothar J., Zimber-Strobl, Ursula, and Zörnig, Martin

Published
2011
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18. A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

Author

Enard, Wolfgang, Gehre, Sabine, Hammerschmidt, Kurt, Hölter, Sabine M., Blass, Torsten, Somel, Mehmet, Brückner, Martina K., Schreiweis, Christiane, Winter, Christine, Sohr, Reinhard, Becker, Lore, Wiebe, Victor, Nickel, Birgit, Giger, Thomas, Müller, Uwe, Groszer, Matthias, Adler, Thure, Aguilar, Antonio, Bolle, Ines, Calzada-Wack, Julia, Dalke, Claudia, Ehrhardt, Nicole, Favor, Jack, Fuchs, Helmut, Gailus-Durner, Valérie, Hans, Wolfgang, Hölzlwimmer, Gabriele, Javaheri, Anahita, Kalaydjiev, Svetoslav, Kallnik, Magdalena, Kling, Eva, Kunder, Sandra, Moßbrugger, Ilona, Naton, Beatrix, Racz, Ildikó, Rathkolb, Birgit, Rozman, Jan, Schrewe, Anja, Busch, Dirk H., Graw, Jochen, Ivandic, Boris, Klingenspor, Martin, Klopstock, Thomas, Ollert, Markus, Quintanilla-Martinez, Leticia, Schulz, Holger, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, Fisher, Simon E., Morgenstern, Rudolf, Arendt, Thomas, Hrabé de Angelis, Martin, Fischer, Julia, Schwarz, Johannes, and Pääbo, Svante

Published
2009
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19. Rapamycin extends murine lifespan but has limited effects on aging

Author

Neff, Frauke, Flores-Dominguez, Diana, Ryan, Devon P., Horsch, Marion, Schroder, Susanne, Adler, Thure, Afonso, Luciana Caminha, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Garrett, Lillian, Hans, Wolfgang, Hettich, Moritz M., Holtmeier, Richard, Holter, Sabine M., Moreth, Kristin, Prehn, Cornelia, Puk, Oliver, Racz, Ildiko, Rathkolb, Birgit, Rozman, Jan, Naton, Beatrix, Ordemann, Rainer, Adamski, Jerzy, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H., Ehninger, Gerhard, Graw, Jochen, Hofler, Heinz, Klingenspor, Martin, Klopstock, Thomas, Ollert, Markus, Stypmann, Jorg, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, Fuchs, Helmut, Gailus-Durner, Valerie, de Angelis, Martin Hrabe, and Ehninger, Dan

Subjects
Aging -- Research, Rapamycin -- Dosage and administration -- Physiological aspects, Life spans (Biology) -- Research, Health care industry
Abstract

Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest [...]

Published
2013
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20. Innovations in phenotyping of mouse models in the German Mouse Clinic

Author

Fuchs, Helmut, Gailus-Durner, Valérie, Neschen, Susanne, Adler, Thure, Afonso, Luciana Caminha, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Bohla, Alexander, Calzada-Wack, Julia, Cohrs, Christian, Dewert, Anna, Fridrich, Barbara, Garrett, Lillian, Glasl, Lisa, Götz, Alexander, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Hurt, Anja, Janas, Eva, Janik, Dirk, Kahle, Melanie, Kistler, Martin, Klein-Rodewald, Tanja, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Marschall, Susan, Micklich, Kateryna, Möller, Gabriele, Naton, Beatrix, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Räß, Michael, Rathkolb, Birgit, Rozman, Jan, Scheerer, Markus, Schiller, Evelyn, Schrewe, Anja, Steinkamp, Ralph, Stöger, Claudia, Sun, Minxuan, Szymczak, Wilfried, Treise, Irina, Vargas Panesso, Ingrid Liliana, Vernaleken, Alexandra M., Willershäuser, Monja, Wolff-Muscate, Annemarie, Zeh, Ramona, Adamski, Jerzy, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H., Eickelberg, Oliver, Favor, Jack, Graw, Jochen, Höfler, Heinz, Höschen, Christoph, Katus, Hugo, Klingenspor, Martin, Klopstock, Thomas, Neff, Frauke, Ollert, Markus, Schulz, Holger, Stöger, Tobias, Wolf, Eckhard, Wurst, Wolfgang, Yildirim, Ali Önder, Zimmer, Andreas, and Hrabě de Angelis, Martin

Published
2012
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21. Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 416insG mice

Author

Rosemann, Michael, Ivashkevich, Alesia, Favor, Jack, Dalke, Claudia, Hölter, Sabine M., Becker, Lore, Rácz, Ildikó, Bolle, Ines, Klempt, Martina, Rathkolb, Birgit, Kalaydjiev, Svetoslav, Adler, Thure, Aguilar, Antonio, Hans, Wolfgang, Horsch, Marion, Rozman, Jan, Calzada-Wack, Julia, Kunder, Sandra, Naton, Beatrix, Gailus-Durner, Valerie, Fuchs, Helmut, Schulz, Holger, Beckers, Johannes, Busch, Dirk H., Burbach, J. Peter H., Smidt, Marten P., Quintanilla-Martinez, Leticia, Esposito, Irene, Klopstock, Thomas, Klingenspor, Martin, Ollert, Markus, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, Hrabé de Angelis, Martin, Atkinson, Michael, Heinzmann, Ulrich, and Graw, Jochen

Published
2010
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23. Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors

Author

Gispert, Suzana, Parganlija, Dajana, Klinkenberg, Michael, Dröse, Stefan, Wittig, Ilka, Mittelbronn, Michel, Grzmil, Pawel, Koob, Sebastian, Hamann, Andrea, Walter, Michael, Büchel, Finja, Adler, Thure, Hrabé de Angelis, Martin, Busch, Dirk H., Zell, Andreas, Reichert, Andreas S., Brandt, Ulrich, Osiewacz, Heinz D., Jendrach, Marina, and Auburger, Georg

Published
2013
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24. Systemic First-Line Phenotyping

Author

Gailus-Durner*, Valérie, primary, Fuchs*, Helmut, additional, Adler, Thure, additional, Aguilar Pimentel, Antonio, additional, Becker, Lore, additional, Bolle, Ines, additional, Calzada-Wack, Julia, additional, Dalke, Claudia, additional, Ehrhardt, Nicole, additional, Ferwagner, Barbara, additional, Hans, Wolfgang, additional, Hölter, Sabine M., additional, Hölzlwimmer, Gabriele, additional, Horsch, Marion, additional, Javaheri, Anahita, additional, Kallnik, Magdalena, additional, Kling, Eva, additional, Lengger, Christoph, additional, Mörth, Corinna, additional, Mossbrugger, Ilona, additional, Naton, Beatrix, additional, Prehn, Cornelia, additional, Puk, Oliver, additional, Rathkolb, Birgit, additional, Rozman, Jan, additional, Schrewe, Anja, additional, Thiele, Frank, additional, Adamski, Jerzy, additional, Aigner, Bernhard, additional, Behrendt, Heidrun, additional, Busch, Dirk H., additional, Favor, Jack, additional, Graw, Jochen, additional, Heldmaier, Gerhard, additional, Ivandic, Boris, additional, Katus, Hugo, additional, Klingenspor, Martin, additional, Elisabeth Kremmer, Thomas Klopstock, additional, Ollert, Markus, additional, Quintanilla-Martinez, Leticia, additional, Schulz, Holger, additional, Wolf, Eckhard, additional, Wurst, Wolfgang, additional, and de Angelis, Martin Hrabé, additional

Published
2009
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25. A Novel N-Ethyl-N-Nitrosourea–Induced Mutation in Phospholipase Cγ2 Causes Inflammatory Arthritis, Metabolic Defects, and Male Infertility in Vitro in A Murine Model

Author

Abe, Koichiro, Fuchs, Helmut, Boersma, Auke, Hans, Wolfgang, Yu, Philipp, Kalaydjiev, Svetoslav, Klaften, Matthias, Adler, Thure, Calzada-Wack, Julia, Mossbrugger, Ilona, Rathkolb, Birgit, Rozman, Jan, Prehn, Cornelia, Maraslioglu, Miriam, Kametani, Yoshie, Shimada, Shin, Adamski, Jerzy, Busch, Dirk H., Esposito, Irene, Klingenspor, Martin, Wolf, Eckhard, Wurst, Wolfgang, Gailus-Durner, Valerie, Katan, Matilda, Marschall, Susan, Soewarto, Dian, Wagner, Sibylle, and de Angelis, Martin Hrabě

Published
2011
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26. Expression Pattern of G Protein-Coupled Receptor 30 in LacZ Reporter Mice

Author

Isensee, Jörg, Meoli, Luca, Zazzu, Valeria, Nabzdyk, Christoph, Witt, Henning, Soewarto, Dian, Effertz, Karin, Fuchs, Helmut, Gailus-Durner, Valérie, Busch, Dirk, Adler, Thure, de Angelis, Martin Hrabé, Irgang, Markus, Otto, Christiane, and Noppinger, Patricia Ruiz

Published
2009

27. Claudin-12 is not required for blood–brain barrier tight junction function

Author

Castro Dias, Mariana, Coisne, Caroline, Engelhardt, Britta, Aguilar-Pimentel, Antonio, Adler, Thure, Busch, Dirk H, Spielmann, Nadine, Moreth, Kristin, Hans, Wolfgang, Amarie, Oana, Graw, Jochen, Rozman, Jan, Baden, Pascale, Radc, Ildiko, Neff, Frauke, Calzada-Wack, Julia, Rathkolb, Birgit, Wolf, Eckhard, Klopstock, Thomas, Wurst, Wolfgang, Beckers, Johannes, Östereicher, Manuela, Miller, Gregor, Enzmann, Gaby, Maier, Holger, Stoeger, Claudia, Leuchtenberger, Stefanie, Gailus-Durner, Valérie, Fuchs, Helmut, Garrett, Lillian, Becker, Lore, Hölter, Sabine M, Consortium, German Mouse Clinic, Hrabě de Angelis, Martin, and Deutsch, Urban

Subjects
Male, 0301 basic medicine, endocrine system diseases, urologic and male genital diseases, lcsh:RC346-429, 0302 clinical medicine, Claudin-12, Gene Knock-In Techniques, Experimental autoimmune encephalomyelitis, Tight junction, General Medicine, ddc, 3. Good health, Cell biology, medicine.anatomical_structure, Neurology, Blood-Brain Barrier, Paracellular transport, Female, tissues, Cell type, Encephalomyelitis, Autoimmune, Experimental, Central nervous system, 610 Medicine & health, Mice, Transgenic, Biology, Blood–brain barrier, digestive system, Tight Junctions, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Animals, ddc:610, Claudin, lcsh:Neurology. Diseases of the nervous system, Neuroinflammation, Blood–brain Barrier, Experimental Autoimmune Encephalomyelitis, Research, Endothelial Cells, medicine.disease, digestive system diseases, Mice, Inbred C57BL, 030104 developmental biology, Claudins, 570 Life sciences, biology, 030217 neurology & neurosurgery
Abstract

Background The blood–brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junctions (TJs) between brain endothelial cells block uncontrolled paracellular diffusion of molecules across the BBB, with claudin-5 being its dominant TJs protein. However, claudin-5 deficient mice still display ultrastructurally normal TJs, suggesting the contribution of other claudins or tight-junction associated proteins in establishing BBB junctional complexes. Expression of claudin-12 at the BBB has been reported, however the exact function and subcellular localization of this atypical claudin remains unknown. Methods We created claudin-12-lacZ-knock-in C57BL/6J mice to explore expression of claudin-12 and its role in establishing BBB TJs function during health and neuroinflammation. We furthermore performed a broad standardized phenotypic check-up of the mouse mutant. Results Making use of the lacZ reporter allele, we found claudin-12 to be broadly expressed in numerous organs. In the CNS, expression of claudin-12 was detected in many cell types with very low expression in brain endothelium. Claudin-12lacZ/lacZ C57BL/6J mice lacking claudin-12 expression displayed an intact BBB and did not show any signs of BBB dysfunction or aggravated neuroinflammation in an animal model for multiple sclerosis. Determining the precise localization of claudin-12 at the BBB was prohibited by the fact that available anti-claudin-12 antibodies showed comparable detection and staining patterns in tissues from wild-type and claudin-12lacZ/lacZ C57BL/6J mice. Conclusions Our present study thus shows that claudin-12 is not essential in establishing or maintaining BBB TJs integrity. Claudin-12 is rather expressed in cells that typically lack TJs suggesting that claudin-12 plays a role other than forming classical TJs. At the same time, in depth phenotypic screening of clinically relevant organ functions of claudin-12lacZ/lacZ C57BL/6J mice suggested the involvement of claudin-12 in some neurological but, more prominently, in cardiovascular functions.

Published
2019
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28. Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase deficiency

Author

Segal, Joanna, primary, Mülleder, Michael, additional, Krüger, Antje, additional, Adler, Thure, additional, Scholze‐Wittler, Manuela, additional, Becker, Lore, additional, Calzada‐Wack, Julia, additional, Garrett, Lillian, additional, Hölter, Sabine M., additional, Rathkolb, Birgit, additional, Rozman, Jan, additional, Racz, Ildiko, additional, Fischer, Ralf, additional, Busch, Dirk H., additional, Neff, Frauke, additional, Klingenspor, Martin, additional, Klopstock, Thomas, additional, Grüning, Nana‐Maria, additional, Michel, Steve, additional, Lukaszewska‐McGreal, Beata, additional, Voigt, Ingo, additional, Hartmann, Ludger, additional, Timmermann, Bernd, additional, Lehrach, Hans, additional, Wolf, Eckhard, additional, Wurst, Wolfgang, additional, Gailus‐Durner, Valérie, additional, Fuchs, Helmut, additional, H. de Angelis, Martin, additional, Schrewe, Heinrich, additional, Yuneva, Mariia, additional, and Ralser, Markus, additional

Published
2019
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30. CRN2 binds to TIMP4 and MMP14 and promotes perivascular invasion of glioblastoma cells

Author

Solga, Roxana, Behrens, Juliane, Ziemann, Anja, Riou, Adrien, Berwanger, Carolin, Becker, Lore, Garrett, Lillian, de Angelis, Martin Hrabe, Fischer, Lisa, Coras, Roland, Barkovits, Katalin, Marcus, Katrin, Mahabir, Esther, Eichinger, Ludwig, Schroeder, Rolf, Noegel, Angelika A., Clemen, Christoph S., Aguilar-Pimentel, Antonio, Schmidt-Weber, Carsten, Klopstock, Thomas, Adler, Thure, Treisel, Irina, Busch, Dirk H., Moreth, Kristin, Hoelter, Sabine M., Zimprich, Annemarie, Wurst, Wolfgang, Amarie, Oana, Graw, Jochen, Rozman, Jan, Calzada-Wack, Julia, Racz, Ildiko, Rathkolb, Birgit, Wolf, Eckhard, Oestereicher, Manuela, Miller, Gregor, Lengger, Christoph, Maier, Holger, Stoeger, Claudia, Leuchtenberger, Stefanie, Gallus-Durner, Valerie, Fuchs, Helmut, Solga, Roxana, Behrens, Juliane, Ziemann, Anja, Riou, Adrien, Berwanger, Carolin, Becker, Lore, Garrett, Lillian, de Angelis, Martin Hrabe, Fischer, Lisa, Coras, Roland, Barkovits, Katalin, Marcus, Katrin, Mahabir, Esther, Eichinger, Ludwig, Schroeder, Rolf, Noegel, Angelika A., Clemen, Christoph S., Aguilar-Pimentel, Antonio, Schmidt-Weber, Carsten, Klopstock, Thomas, Adler, Thure, Treisel, Irina, Busch, Dirk H., Moreth, Kristin, Hoelter, Sabine M., Zimprich, Annemarie, Wurst, Wolfgang, Amarie, Oana, Graw, Jochen, Rozman, Jan, Calzada-Wack, Julia, Racz, Ildiko, Rathkolb, Birgit, Wolf, Eckhard, Oestereicher, Manuela, Miller, Gregor, Lengger, Christoph, Maier, Holger, Stoeger, Claudia, Leuchtenberger, Stefanie, Gallus-Durner, Valerie, and Fuchs, Helmut

Abstract

CRN2 is an actin filament binding protein involved in the regulation of various cellular processes including cell migration and invasion. CRN2 has been implicated in the malignant progression of different types of human cancer. We used CRN2 knock-out mice for analyses as well as for crossbreeding with a Tp53/Pten knock-out glioblastoma mouse model. CRN2 knock-out mice were subjected to a phenotyping screen at the German Mouse Clinic. Murine glioblastoma tissue specimens as well as cultured murine brain slices and glioblastoma cell lines were investigated by immunohistochemistry, immunofluorescence, and cell biological experiments. Protein interactions were studied by immunoprecipitation, pull-down, and enzyme activity assays. CRN2 knock-out mice displayed neurological and behavioural alterations, e.g. reduced hearing sensitivity, reduced acoustic startle response, hypoactivity, and less frequent urination. While glioblastoma mice with or without the additional CRN2 knock-out allele exhibited no significant difference in their survival rates, the increased levels of CRN2 in transplanted glioblastoma cells caused a higher tumour cell encasement of murine brain slice capillaries. We identified two important factors of the tumour microenvironment, the tissue inhibitor of matrix metalloproteinase 4 (TIMP4) and the matrix metalloproteinase 14 (MMP14, synonym: MT1-MMP), as novel binding partners of CRN2. All three proteins mutually interacted and co-localised at the front of lamellipodia, and CRN2 was newly detected in exosomes. On the functional level, we demonstrate that CRN2 increased the secretion of TIMP4 as well as the catalytic activity of MMP14. Our results imply that CRN2 represents a pro-invasive effector within the tumour cell microenvironment of glioblastoma multiforme.

Published
2019

31. A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

Author

Kollmus, Heike, Fuchs, Helmut, Lengger, Christoph, Haselimashhadi, Hamed, Bogue, Molly A., Östereicher, Manuela A., Horsch, Marion, Adler, Thure, Aguilar-Pimentel, Juan Antonio, Amarie, Oana Veronica, Becker, Lore, Beckers, Johannes, Calzada-Wack, Julia, Garrett, Lillian, Hans, Wolfgang, Hölter, Sabine M., Klein-Rodewald, Tanja, Maier, Holger, Mayer-Kuckuk, Philipp, and Miller, Gregor

Subjects
COMPARATIVE studies, ENERGY metabolism, BLOOD testing, BONES, CLINICAL chemistry
Abstract

The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, and pathology were analyzed; in most traits from sixteen females and sixteen males. We identified over 270 parameters that were significantly different between strains. This study highlights the value of the founder and CC strains for phenotype-genotype associations of many genetic traits that are highly relevant to human diseases. All data described here are publicly available from the mouse phenome database for analyses and downloads. [ABSTRACT FROM AUTHOR]

Published
2020
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32. Defective immuno- and thymoproteasome assembly causes severe immunodeficiency

Author

Treise, Irina, primary, Huber, Eva M., additional, Klein-Rodewald, Tanja, additional, Heinemeyer, Wolfgang, additional, Grassmann, Simon A., additional, Basler, Michael, additional, Adler, Thure, additional, Rathkolb, Birgit, additional, Helming, Laura, additional, Andres, Christian, additional, Klaften, Matthias, additional, Landbrecht, Christina, additional, Wieland, Thomas, additional, Strom, Tim M., additional, McCoy, Kathy D., additional, Macpherson, Andrew J., additional, Wolf, Eckhard, additional, Groettrup, Marcus, additional, Ollert, Markus, additional, Neff, Frauke, additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, Hrabě de Angelis, Martin, additional, Groll, Michael, additional, and Busch, Dirk H., additional

Published
2018
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33. The Role of Fibroblast Growth Factor-Binding Protein 1 in Skin Carcinogenesis and Inflammation

Author

Schmidt, Marcel Oliver, primary, Garman, Khalid Ammar, additional, Lee, Yong Gu, additional, Zuo, Chong, additional, Beck, Patrick James, additional, Tan, Mingjun, additional, Aguilar-Pimentel, Juan Antonio, additional, Ollert, Markus, additional, Schmidt-Weber, Carsten, additional, Fuchs, Helmut, additional, Gailus-Durner, Valerie, additional, Hrabe de Angelis, Martin, additional, Tassi, Elena, additional, Riegel, Anna Tate, additional, Wellstein, Anton, additional, Becker, Lore, additional, Vernaleken, Alexandra, additional, Klopstock, Thomas, additional, Adler, Thure, additional, Treise, Irina, additional, Horsch, Marion, additional, Moreth, Kristin, additional, Brommage, Robert, additional, Hans, Wolfgang, additional, Östereicher, Manuela, additional, Steinkamp, Ralph, additional, Lengger, Christoph, additional, Maier, Holger, additional, Stoeger, Claudia, additional, Leuchtenberger, Stefanie, additional, Busch, Dirk H., additional, Beckers, Johannes, additional, Bekeredjian, Raffi, additional, Garrett, Lillian, additional, Hölter, Sabine M., additional, Zimprich, Annemarie, additional, Amarie, Oana, additional, Wurst, Wolfgang, additional, Graw, Jochen, additional, Rozman, Jan, additional, Calzada-Wack, Julia, additional, da Silva-Buttkus, Patricia, additional, Neff, Frauke, additional, Klingenspor, Martin, additional, Racz, Ildiko, additional, Zimmer, Andreas, additional, Rathkolb, Birgit, additional, and Wolf, Eckhard, additional

Published
2018
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34. The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations

Author

Fuchs, Helmut, Sabrautzki, Sibylle, Przemeck, Gerhard K. H., Leuchtenberger, Stefanie, Lorenz-Depiereux, Bettina, Becker, Lore, Rathkolb, Birgit, Horsch, Marion, Garrett, Lillian, Östereicher, Manuela A., Hans, Wolfgang, Abe, Koichiro, Sagawa, Nobuho, Rozman, Jan, Vargas-Panesso, Ingrid L., Sandholzer, Michael, Lisse, Thomas S., Adler, Thure, Aguilar-Pimentel, Juan Antonio, Calzada-Wack, Julia, Ehrhard, Nicole, Elvert, Ralf, Gau, Christine, Hölter, Sabine M., Micklich, Katja, Moreth, Kristin, Prehn, Cornelia, Puk, Oliver, Racz, Ildiko, Stoeger, Claudia, Vernaleken, Alexandra, Michel, Dian, Diener, Susanne, Wieland, Thomas, Adamski, Jerzy, Bekeredjian, Raffi, Busch, Dirk H., Favor, John, Graw, Jochen, Klingenspor, Martin, Lengger, Christoph, Maier, Holger, Neff, Frauke, Ollert, Markus, Stoeger, Tobias, Yildirim, Ali Önder, Strom, Tim M., Zimmer, Andreas, Wolf, Eckhard, Wurst, Wolfgang, Klopstock, Thomas, Beckers, Johannes, Gailus-Durner, Valerie, and Hrabé de Angelis, Martin

Subjects
Male, mouse model, genetics [Energy Metabolism], QH426-470, Investigations, pleitropy, Kidney, Kidney Function Tests, Bone and Bones, metabolism [Bone and Bones], Mice, systemic phenotype, ddc:570, pathology [Osteitis Deformans], Genetics, Animals, physiopathology [Kidney], Exome, Genetic Association Studies, Skeleton, Glycoproteins, Mice, Knockout, metabolism [Osteitis Deformans], SCUBE3, Gene Expression Profiling, Calcium-Binding Proteins, metabolism [Kidney], Chromosome Mapping, High-Throughput Nucleotide Sequencing, Osteitis Deformans, abnormalities [Skeleton], Disease Models, Animal, genetics [Osteitis Deformans], Phenotype, Mutation, Scube3 protein, mouse, Female, genetics [Glycoproteins], Paget disease of bone (PDB), Energy Metabolism
Abstract

The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein) family consists of three independent members, Scube1-3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3(N294K/N294K)), which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC). Scube3(N294K/N294K) mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB), associated with the chromosomal region of human SCUBE3 In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3(N294K/N294K) mice. The Scube3(N294K/N294K) mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function.

Published
2016
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35. Data on the effects of eIF6 downmodulation on the proportions of innate and adaptive immune system cell subpopulations and on thymocyte maturation

Author

Manfrini, Nicola, primary, Ricciardi, Sara, additional, Miluzio, Annarita, additional, Fedeli, Maya, additional, Scagliola, Alessandra, additional, Gallo, Simone, additional, Adler, Thure, additional, Busch, Dirk H., additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, de Angelis, Martin Hrabě, additional, and Biffo, Stefano, additional

Published
2017
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36. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice

Author

Ganguly, Koustav, primary, Ettehadieh, Dariusch, additional, Upadhyay, Swapna, additional, Takenaka, Shinji, additional, Adler, Thure, additional, Karg, Erwin, additional, Krombach, Fritz, additional, Kreyling, Wolfgang G., additional, Schulz, Holger, additional, Schmid, Otmar, additional, and Stoeger, Tobias, additional

Published
2017
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37. Extensive phenotypic characterization of a new transgenic mouse reveals pleiotropic perturbations in physiology due to mesenchymal hGH minigene expression

Author

Kaklamanos, Aimilios, primary, Rozman, Jan, additional, Roulis, Manolis, additional, Karagianni, Niki, additional, Armaka, Maria, additional, Wu, Moya, additional, Brachthäuser, Laura, additional, Calzada-Wack, Julia, additional, Horsch, Marion, additional, Beckers, Johannes, additional, Rathkolb, Birgit, additional, Adler, Thure, additional, Neff, Frauke, additional, Wolf, Eckhard, additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, de Angelis, Martin Hrabe, additional, and Kollias, George, additional

Published
2017
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39. Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity

Author

Keeney, J. G., O'Bleness, M. S., Horsch, M., Consortium, German Mouse Clinic, Beckers, J., Wurst, W., Klingenspor, M., Restrepo, D., de Angelis, M Hrabě, Sikela, J. M., Adler, Thure, Aguilar-Pimentel, Antonio, Anderson, N., Amarie, Oana, Becker, Lore, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H, Eickelberg, Oliver, Garrett, Lillian, Graw, Jochen, Hans, Wolfgang, Hölter, Sabine M, Davis, J. M., Horsch, Marion, Janik, Dirk, Klingenspor, Martin, Klopstock, Thomas, Moreth, Kristin, Neff, Frauke, Ollert, Markus, Puk, Oliver, Rácz, Ildikó, Rathkolb, Birgit, Arevalo, N., Rozman, Jan, Stöger, Tobias, Wolf, Eckhard, Yildrim, Ali Önder, Zimmer, Andreas, de Angelis, Martin Hrabe, Gailus-Durner, Valérie, Fuchs, Helmut, Busquet, N., Chick, W., Rozman, J., Hölter, S. M., and Garrett, L.

Subjects
Blood Glucose, Male, medicine.medical_specialty, Protein domain, Gene Dosage, Mice, Transgenic, Biology, Hyperkinesis, Gene dosage, genetics [Hyperkinesis], Article, Gene Knockout Techniques, Mice, ddc:570, Internal medicine, Genetics, medicine, Animals, genetics [DNA Primers], DNA Primers, metabolism [Blood Glucose], Gene Expression Profiling, growth & development [Brain], Brain, Calorimetry, Indirect, genetics [Fertility], Human brain, Organ Size, Phenotype, Biological Evolution, DUF1220, Protein Structure, Tertiary, Gene expression profiling, medicine.anatomical_structure, Endocrinology, Fertility, Liver, Area Under Curve, Brain size, Liver function, genetics [Mice, Transgenic], metabolism [Liver]
Abstract

Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question, we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ 2 = 19.1, df = 2, p = 7.0 × 10−5). Further extensive phenotypic analyses suggest hyperactivity (p

Published
2014
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40. CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Come, Christophe, Cvrljevic, Anna, Khan, Mohd Moin, Treise, Irina, Adler, Thure, Aguilar-Pimentel, Juan Antonio, Au-Yeung, Byron, Sittig, Eleonora, Laajala, Teemu Daniel, Chen, Yiling, Oeder, Sebastian, Calzada-Wack, Julia, Horsch, Marion, Aittokallio, Tero, Busch, Dirk H., Ollert, Markus W., Neff, Frauke, Beckers, Johannes, Gailus-Durner, Valerie, Fuchs, Helmut, de Angelis, Martin Hrabe, Chen, Zhi, Lahesmaa, Riitta, Westermarck, Jukka, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Come, Christophe, Cvrljevic, Anna, Khan, Mohd Moin, Treise, Irina, Adler, Thure, Aguilar-Pimentel, Juan Antonio, Au-Yeung, Byron, Sittig, Eleonora, Laajala, Teemu Daniel, Chen, Yiling, Oeder, Sebastian, Calzada-Wack, Julia, Horsch, Marion, Aittokallio, Tero, Busch, Dirk H., Ollert, Markus W., Neff, Frauke, Beckers, Johannes, Gailus-Durner, Valerie, Fuchs, Helmut, de Angelis, Martin Hrabe, Chen, Zhi, Lahesmaa, Riitta, and Westermarck, Jukka

Abstract

The oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A ( CIP2A) is overexpressed in most malignancies and is an obvious candidate target protein for future cancer therapies. However, the physiological importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A regulates immune responses, we investigated the role of CIP2A in normal immune system development and during immune response in vivo. We show that CIP2A-deficient mice (CIP2A(HOZ)) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2A(HOZ) mice display an impaired adaptive immune response that is combined with decreased frequency of both CD4(+) T-cells and CD8(+) effector T-cells. Importantly, the cell autonomous effect of CIP2A deficiency for T-cell activation was confirmed. Induction of CIP2A expression during T-cell activation was dependent on Zap70 activity. Thus, we reveal CIP2A as a hitherto unrecognized mediator of T-cell activation during adaptive immune response. These results also reveal CIP2A(HOZ) as a possible novel mouse model for studying the role of PP2A activity in immune regulation. On the other hand, the results also indicate that CIP2A targeting cancer therapies would not cause serious immunological side-effects.

Published
2016

41. CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection

Author

Côme, Christophe, primary, Cvrljevic, Anna, additional, Khan, Mohd Moin, additional, Treise, Irina, additional, Adler, Thure, additional, Aguilar-Pimentel, Juan Antonio, additional, Au-Yeung, Byron, additional, Sittig, Eleonora, additional, Laajala, Teemu Daniel, additional, Chen, Yiling, additional, Oeder, Sebastian, additional, Calzada-Wack, Julia, additional, Horsch, Marion, additional, Aittokallio, Tero, additional, Busch, Dirk H., additional, Ollert, Markus W., additional, Neff, Frauke, additional, Beckers, Johannes, additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, de Angelis, Martin Hrabě, additional, Chen, Zhi, additional, Lahesmaa, Riitta, additional, and Westermarck, Jukka, additional

Published
2016
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42. Lymphotoxin β receptor signalling executesHelicobacter pylori-driven gastric inflammation in a T4SS-dependent manner

Author

Mejías-Luque, Raquel, primary, Zöller, Jessica, additional, Anderl, Florian, additional, Loew-Gil, Elena, additional, Vieth, Michael, additional, Adler, Thure, additional, Engler, Daniela B, additional, Urban, Sabine, additional, Browning, Jeffrey L, additional, Müller, Anne, additional, Gerhard, Markus, additional, and Heikenwalder, Mathias, additional

Published
2016
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43. Generation and Standardized, Systemic Phenotypic Analysis of Pou3f3L423P Mutant Mice

Author

Kumar, Sudhir, primary, Rathkolb, Birgit, additional, Kemter, Elisabeth, additional, Sabrautzki, Sibylle, additional, Michel, Dian, additional, Adler, Thure, additional, Becker, Lore, additional, Beckers, Johannes, additional, Busch, Dirk H., additional, Garrett, Lillian, additional, Hans, Wolfgang, additional, Hölter, Sabine M., additional, Horsch, Marion, additional, Klingenspor, Martin, additional, Klopstock, Thomas, additional, Rácz, Ildikó, additional, Rozman, Jan, additional, Vargas Panesso, Ingrid Liliana, additional, Vernaleken, Alexandra, additional, Zimmer, Andreas, additional, Fuchs, Helmut, additional, Gailus-Durner, Valérie, additional, Hrabě de Angelis, Martin, additional, Wolf, Eckhard, additional, and Aigner, Bernhard, additional

Published
2016
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44. Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice.

Author

Kan Xie, Ryan, Devon P., Pearson, Brandon L., Henzel, Kristin S., Neff, Frauke, Vidal, Ramon O., Hennion, Magali, Lehmann, Isabelle, Schleif, Melvin, Schröder, Susanne, Adler, Thure, Rathkolb, Birgit, Rozman, Jan, Schütz, Anna-Lena, Prehn, Cornelia, Mickael, Michel E., Weiergräber, Marco, Adamski, Jerzy, Busch, Dirk H., and Ehninger, Gerhard

Subjects
ANIMAL models for aging, EPIGENETICS, LABORATORY mice, LONGEVITY, LIFE spans
Abstract

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice. [ABSTRACT FROM AUTHOR]

Published
2018
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45. Longitudinal Frequencies of Blood Leukocyte Subpopulations Differ between NOD and NOR Mice but Do Not Predict Diabetes in NOD Mice

Author

Telieps, Tanja, primary, Köhler, Meike, additional, Treise, Irina, additional, Foertsch, Katharina, additional, Adler, Thure, additional, Busch, Dirk H., additional, Hrabě de Angelis, Martin, additional, Verschoor, Admar, additional, Adler, Kerstin, additional, Bonifacio, Ezio, additional, and Ziegler, Anette-Gabriele, additional

Published
2016
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46. Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers

Author

Deng, Tao, primary, Zhu, Z. Iris, additional, Zhang, Shaofei, additional, Postnikov, Yuri, additional, Huang, Di, additional, Horsch, Marion, additional, Furusawa, Takashi, additional, Beckers, Johannes, additional, Rozman, Jan, additional, Klingenspor, Martin, additional, Amarie, Oana, additional, Graw, Jochen, additional, Rathkolb, Birgit, additional, Wolf, Eckhard, additional, Adler, Thure, additional, Busch, Dirk H., additional, Gailus-Durner, Valérie, additional, Fuchs, Helmut, additional, Hrabě de Angelis, Martin, additional, van der Velde, Arjan, additional, Tessarollo, Lino, additional, Ovcherenko, Ivan, additional, Landsman, David, additional, and Bustin, Michael, additional

Published
2015
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48. Pleiotropic Functions for Transcription Factor Zscan10

Author

Kraus, Petra, primary, V, Sivakamasundari, additional, Yu, Hong Bing, additional, Xing, Xing, additional, Lim, Siew Lan, additional, Adler, Thure, additional, Pimentel, Juan Antonio Aguilar, additional, Becker, Lore, additional, Bohla, Alexander, additional, Garrett, Lillian, additional, Hans, Wolfgang, additional, Hölter, Sabine M., additional, Janas, Eva, additional, Moreth, Kristin, additional, Prehn, Cornelia, additional, Puk, Oliver, additional, Rathkolb, Birgit, additional, Rozman, Jan, additional, Adamski, Jerzy, additional, Bekeredjian, Raffi, additional, Busch, Dirk H., additional, Graw, Jochen, additional, Klingenspor, Martin, additional, Klopstock, Thomas, additional, Neff, Frauke, additional, Ollert, Markus, additional, Stoeger, Tobias, additional, Yildrim, Ali Önder, additional, Eickelberg, Oliver, additional, Wolf, Eckhard, additional, Wurst, Wolfgang, additional, Fuchs, Helmut, additional, Gailus-Durner, Valérie, additional, de Angelis, Martin Hrabě, additional, Lufkin, Thomas, additional, and Stanton, Lawrence W., additional

Published
2014
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49. Der Streptozotozin-induzierte Diabetes in der transgenen CD4/DR17-Maus

Author

Adler, Thure and Universität Leipzig

Subjects
Medizin, Streptozotozin,STZ,Diabetes mellitus,Tiermodell, transgen,CD4,DR17,Anti-CD4 Therapie,CD4/DR17-Maus,CD4/DR3-Maus, Typ 1 Diabetes, Diabetes, ddc:610, Biologie, Tiermedizin
Abstract

Zusammenfassung Thure Adler Der Streptozotozin-induzierte Diabetes in der transgenen CD4/DR17-Maus Aus dem Institut für Immunologie der Veterinärmedizinischen Fakultät und dem Institut für Klinische Immunologie und Transfusionsmedizin der Medizinischen Fakultät der Universität Leipzig, 80 Seiten, 24 Abbildungen, 20 Tabellen, 217 Literaturangaben Die Verwendung transgener Tiere, die humane Moleküle exprimieren, gewinnt zunehmend an Bedeutung bei der Erforschung der Funktionen solcher Moleküle in Krankheitsprozessen und bei der experimentellen Erprobung neuartiger Therapieverfahren, in denen solche Moleküle die Zielstrukturen darstellen. In der vorliegenden Arbeit wurde die CD4/DR17-Maus, welche das humane CD4- und das DR17-Molekül exprimiert, im MLD-STZ-induzierten Diabetes, einem Tiermodell für den Typ 1 Diabetes, eingesetzt. Die funktionelle Beteiligung der Transgene wurde durch einen Vergleich mit Segreganten untersucht, denen die Transgene teilweise fehlen. Als klinische Parameter sind Blutglukose und Glukosetoleranz erfaßt worden, histopathologisch wurden Insulitis und Insulingehalt der Inselzellen bestimmt. Ferner wurde getestet, ob sich durch Verabreichung von monoklonalen Antikörpern, die gegen das transgene hCD4- oder gegen das CD8-Molekül gerichtet sind, dieser STZ-induzierte Diabetes beeinflussen läßt. Mit Hilfe der durchflußzytometrischen Immunfluoreszenzanalyse von Blutzellen wurde zusätzlich überprüft, ob Veränderungen auf T-Zellen hinsichtlich der Expression der Aktivierungsmarker CD25, CD69 und CD71 während des STZ-induzierten Diabetes auftreten. Es wurde gezeigt, dass die CD4/DR17-transgene Maus nach der Behandlung mit mehrfachen subdiabetogenen Dosen von Streptozotozin eine transiente Hyperglykämie entwickelt, die mit einer verringerten Glukosetoleranz sowie Insulitiden und einem Rückgang des Insulingehaltes in den Langerhans’schen Inseln einhergeht. Vergleiche mit Segreganten zeigen, dass die Expression beider transgener Merkmale zur maximalen Ausprägung einer schwergradigen Insulitis beiträgt. Die Anwendung von monoklonalen Antikörpern gegen das transgene hCD4-Molekül nach Beginn der STZ-Behandlung hat den Diabetes nicht wirkungsvoll verzögert. Dagegen milderte eine Behandlung mit Antikörpern, die gegen das CD8-Molekül gerichtet sind, den Diabetesverlauf. Während des STZ-Diabetes veränderte sich die Expression von Aktivierungsmarkern auf Lymphozyten des peripheren Blutes nicht signifikant. Die Arbeit belegt, dass die CD4/DR17-Maus suszeptibel gegenüber der Induktion eines experimentellen Diabetes mit mehrfachen subdiabetogenen Dosen von Streptozotozin ist. Die transgenen Moleküle hCD4 und DR17 sind dabei am Krankheitsprozeß beteiligt. Summary Thure Adler The streptozotocin-induced diabetes in the transgenic CD4/DR17 mouse From the Institute of Immunology, Faculty of Veterinary Medicine and the Institute of Clinical Immunology and Transfusion Medicine, Faculty of Medicine, University of Leipzig 80 pages, 24 figures, 20 tables, 217 references Today, transgenic animals that express human molecules are getting important tools in functional studies and experimental, therapeutical attempts, that target these molecules. In this study, the CD4/DR17 mouse expressing the human CD4 and the human DR17 molecules and with a defective murine CD4 gene, was used in the multiple low-dose streptozotocin-induced (MLD-STZ) diabetes model, a model for type 1 diabetes. The functional involvement of the transgenic molecules in the development of the MLD-STZ-diabetes was analysed by comparing CD4/DR17 mice and segregants that lack one or more of the transgenes. The described parameters included the measurement of blood glucose levels and oral glucose tolerance tests, histopathologically grading of insulitis and determination of the content of insulin in pancreatic islets by immunohistological methods. In addition, the model was used to test the potential therapeutic effect of the administration of monoclonal antibodies against hCD4 or CD8. Furthermore, alterations of the expression of the activation markers CD25, CD69 and CD71 during the experimentally induced diabetes has been measured by FACS analysis. The study shows, that CD4/DR17 mice develop a transient hyperglycemia after MLD-STZ treatment, accompanied by a reduced tolerance to oral glucose, insulitis and the reduction of the content of insulin in the pancreatic islets. The full incidence of insulitis requires the expression of both transgenes. The treatment performed with monoclonal antibodies against the transgenic hCD4 after STZ-treatment could not meliorate the diabetic course, while the treatment with anti CD8 antibodies moderated the diabetic process. After STZ-treatment the expression of activation marker of peripheral T-cells did not alter significantly. Thus, the CD4/DR17 mouse is shown to be susceptible to the induction of experimental diabetes with MLD-STZ. The transgenic molecules CD4 and DR17 are involved in the pathogenesis of the disease.

Published
2003

50. Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells

Author

Raab, Monika, Kappel, Sven, Krämer, Andrea, Sanhaji, Mourad, Matthess, Yves, Kurunci-Csacsko, Elisabeth, Calzada-Wack, Julia, Rathkolb, Birgit, Rozman, Jan, Adler, Thure, Busch, Dirk H., Esposito, Irene, Fuchs, Helmut, Gailus-Durner, Valérie, Klingenspor, Martin, Wolf, Eckhard, Sänger, Nicole, Prinz, Florian, Hrabé de Angelis, Martin, Seibler, Jost, Yuan, Juping, Bergmann, Martin, Knecht, Rainald, Kreft, Bertolt, Strebhardt, Klaus, Raab, Monika, Kappel, Sven, Krämer, Andrea, Sanhaji, Mourad, Matthess, Yves, Kurunci-Csacsko, Elisabeth, Calzada-Wack, Julia, Rathkolb, Birgit, Rozman, Jan, Adler, Thure, Busch, Dirk H., Esposito, Irene, Fuchs, Helmut, Gailus-Durner, Valérie, Klingenspor, Martin, Wolf, Eckhard, Sänger, Nicole, Prinz, Florian, Hrabé de Angelis, Martin, Seibler, Jost, Yuan, Juping, Bergmann, Martin, Knecht, Rainald, Kreft, Bertolt, and Strebhardt, Klaus

Abstract

High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions.

Published
2011

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