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6. Impact of spaceflight on the murine thymus and mitigation by exposure to artificial gravity during spaceflight

Author

Horie, Kenta, primary, Kato, Tamotsu, additional, Kudo, Takashi, additional, Sasanuma, Hiroki, additional, Miyauchi, Maki, additional, Akiyama, Nobuko, additional, Miyao, Takahisa, additional, Seki, Takao, additional, Ishikawa, Tatsuya, additional, Takakura, Yuki, additional, Shirakawa, Masaki, additional, Shiba, Dai, additional, Hamada, Michito, additional, Jeon, Hyojung, additional, Yoshida, Nobuaki, additional, Inoue, Jun-ichiro, additional, Muratani, Masafumi, additional, Takahashi, Satoru, additional, Ohno, Hiroshi, additional, and Akiyama, Taishin, additional

Published
2019
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9. Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire)

Author

Horie, Kenta, primary, Kudo, Takashi, additional, Yoshinaga, Riko, additional, Akiyama, Nobuko, additional, Sasanuma, Hiroki, additional, Kobayashi, Tetsuya J., additional, Shimbo, Miki, additional, Jeon, Hyojung, additional, Miyao, Takahisa, additional, Miyauchi, Maki, additional, Shirakawa, Masaki, additional, Shiba, Dai, additional, Yoshida, Nobuaki, additional, Muratani, Masafumi, additional, Takahashi, Satoru, additional, and Akiyama, Taishin, additional

Published
2018
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10. RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production.

Author

Sasanuma, Hiroki, Ozawa, Manabu, and Yoshida, Nobuaki

Subjects
*CARRIER proteins, *PROTEIN binding, *ANTIBODY formation, *RNA-binding proteins
Abstract

The RNA-binding protein polypyrimidine tract-binding protein-1 (Ptbp1) binds to the pyrimidine-rich sequence of target RNA and controls gene expression via post-transcriptional regulation such as alternative splicing. Although Ptbp1 is highly expressed in B lymphocytes, its role to date is largely unknown. To clarify the role of Ptbp1 in B-cell development and function, we generated B-cell-specific Ptbp1-deficient (P1BKO) mice. B-cell development in the bone marrow, spleen and peritoneal cavity of the P1BKO mice was nearly normal. However, the P1BKO mice had significantly lower levels of natural antibodies in serum compared with those of the control mice. To investigate the effect of Ptbp1 deficiency on the immune response in vivo, we immunized the P1BKO mice with T-cell-independent type-2 (TI-2) antigen NP-Ficoll and T-cell-dependent (TD) antigen NP-CGG. We found that B-cell-specific Ptbp1 deficiency causes an immunodeficiency phenotype due to defective production of antibody against both TI-2 and TD antigen. This immunodeficiency was accompanied by impaired B-cell receptor (BCR)-mediated B-cell activation and plasmablast generation. These findings demonstrate that Ptbp1 is essential for the humoral immune response. [ABSTRACT FROM AUTHOR]

Published
2019
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11. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

Author

Shimbo, Miki, Kudo, Takashi, Hamada, Michito, Jeon, Hyojung, Imamura, Yuki, Asano, Keigo, Okada, Risa, Tsunakawa, Yuki, Mizuno, Seiya, Yagami, Kenichi, Ishikawa, Chihiro, Li, Haiyan, Shiga, Takashi, Ishida, Junji, Hamada, Juri, Murata, Kazuya, Ishimaru, Tomohiro, Hashimoto, Misuzu, Fukamizu, Akiyoshi, Yamane, Mutsumi, Ikawa, Masahito, Morita, Hironobu, Shinohara, Masahiro, Asahara, Hiroshi, Akiyama, Taishin, Akiyama, Nobuko, Sasanuma, Hiroki, Yoshida, Nobuaki, Zhou, Rui, Wang, Ying-Ying, Ito, Taito, Kokubu, Yuko, Noguchi, Takaaki, K., Ishimine, Hisako, Kurisaki, Akira, Shiba, Dai, Mizuno, Hiroyasu, Shirakawa, Masaki, Ito, Naoki, Takeda, Shin, Takahashi, Satoru, 新保, 未来, 工藤, 崇, 濱田, 理人, 今村, 優希, 浅野, 圭吾, 岡田, 理沙, 綱川, 祐貴, 水野, 聖哉, 八神, 健一, 石川, 千尋, 志賀, 隆, 石田, 純治, 濱田, 樹理, 村田, 知弥, 石丸, 友博, 橋本, 美涼, 深水, 昭吉, 山根, 睦, 伊川, 正人, 森田, 啓之, 篠原, 正浩, 浅原, 弘嗣, 秋山, 泰身, 秋山, 伸子, 笹沼, 寛樹, 吉田, 進昭, 伊藤, 泰斗, 國分, 優子, 野口, 隆明, 石嶺, 久子, 栗崎, 晃, 芝, 大, 水野, 浩靖, 白川, 正輝, 伊藤, 尚基, 武田, 伸一, 高橋, 智, Shimbo, Miki, Kudo, Takashi, Hamada, Michito, Jeon, Hyojung, Imamura, Yuki, Asano, Keigo, Okada, Risa, Tsunakawa, Yuki, Mizuno, Seiya, Yagami, Kenichi, Ishikawa, Chihiro, Li, Haiyan, Shiga, Takashi, Ishida, Junji, Hamada, Juri, Murata, Kazuya, Ishimaru, Tomohiro, Hashimoto, Misuzu, Fukamizu, Akiyoshi, Yamane, Mutsumi, Ikawa, Masahito, Morita, Hironobu, Shinohara, Masahiro, Asahara, Hiroshi, Akiyama, Taishin, Akiyama, Nobuko, Sasanuma, Hiroki, Yoshida, Nobuaki, Zhou, Rui, Wang, Ying-Ying, Ito, Taito, Kokubu, Yuko, Noguchi, Takaaki, K., Ishimine, Hisako, Kurisaki, Akira, Shiba, Dai, Mizuno, Hiroyasu, Shirakawa, Masaki, Ito, Naoki, Takeda, Shin, Takahashi, Satoru, 新保, 未来, 工藤, 崇, 濱田, 理人, 今村, 優希, 浅野, 圭吾, 岡田, 理沙, 綱川, 祐貴, 水野, 聖哉, 八神, 健一, 石川, 千尋, 志賀, 隆, 石田, 純治, 濱田, 樹理, 村田, 知弥, 石丸, 友博, 橋本, 美涼, 深水, 昭吉, 山根, 睦, 伊川, 正人, 森田, 啓之, 篠原, 正浩, 浅原, 弘嗣, 秋山, 泰身, 秋山, 伸子, 笹沼, 寛樹, 吉田, 進昭, 伊藤, 泰斗, 國分, 優子, 野口, 隆明, 石嶺, 久子, 栗崎, 晃, 芝, 大, 水野, 浩靖, 白川, 正輝, 伊藤, 尚基, 武田, 伸一, and 高橋, 智

Abstract

The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module (“Kibo”) on the International Space Station. The CBEF provides “space-based controls” by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments., full name: Takeda, Shinichi, Physical characteristics: Original contains illustrations, full name: 武田, 伸一, 形態: 図版あり

Published
2016

12. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

Author

Shimbo, Miki, primary, Kudo, Takashi, additional, Hamada, Michito, additional, Jeon, Hyojung, additional, Imamura, Yuki, additional, Asano, Keigo, additional, Okada, Risa, additional, Tsunakawa, Yuki, additional, Mizuno, Seiya, additional, Yagami, Ken-ichi, additional, Ishikawa, Chihiro, additional, Li, Haiyan, additional, Shiga, Takashi, additional, Ishida, Junji, additional, Hamada, Juri, additional, Murata, Kazuya, additional, Ishimaru, Tomohiro, additional, Hashimoto, Misuzu, additional, Fukamizu, Akiyoshi, additional, Yamane, Mutsumi, additional, Ikawa, Masahito, additional, Morita, Hironobu, additional, Shinohara, Masahiro, additional, Asahara, Hiroshi, additional, Akiyama, Taishin, additional, Akiyama, Nobuko, additional, Sasanuma, Hiroki, additional, Yoshida, Nobuaki, additional, Zhou, Rui, additional, Wang, Ying-Ying, additional, Ito, Taito, additional, Kokubu, Yuko, additional, Noguchi, Taka-aki K., additional, Ishimine, Hisako, additional, Kurisaki, Akira, additional, Shiba, Dai, additional, Mizuno, Hiroyasu, additional, Shirakawa, Masaki, additional, Ito, Naoki, additional, Takeda, Shin, additional, and Takahashi, Satoru, additional

Published
2016
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13. Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice

Author

Tateishi, Ryosuke, primary, Akiyama, Nobuko, additional, Miyauchi, Maki, additional, Yoshinaga, Riko, additional, Sasanuma, Hiroki, additional, Kudo, Takashi, additional, Shimbo, Miki, additional, Shinohara, Masahiro, additional, Obata, Koji, additional, Inoue, Jun-ichiro, additional, Shirakawa, Masaki, additional, Shiba, Dai, additional, Asahara, Hiroshi, additional, Yoshida, Nobuaki, additional, Takahashi, Satoru, additional, Morita, Hironobu, additional, and Akiyama, Taishin, additional

Published
2015
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15. Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes

Author

Shin, Masashi, primary, Ohte, Satoshi, additional, Fukuda, Toru, additional, Sasanuma, Hiroki, additional, Yoneyama, Katsumi, additional, Kokabu, Shoichiro, additional, Miyamoto, Arei, additional, Tsukamoto, Sho, additional, Hohjoh, Hirohiko, additional, Jimi, Eijiro, additional, and Katagiri, Takenobu, additional

Published
2012
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16. Identification and functional analysis of Zranb2 as a novel Smad‐binding protein that suppresses BMP signaling

Author

Ohte, Satoshi, primary, Kokabu, Shoichiro, additional, Iemura, Shun‐ichiro, additional, Sasanuma, Hiroki, additional, Yoneyama, Katsumi, additional, Shin, Masashi, additional, Suzuki, Seiya, additional, Fukuda, Toru, additional, Nakamura, Yukio, additional, Jimi, Eijiro, additional, Natsume, Toru, additional, and Katagiri, Takenobu, additional

Published
2012
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17. A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H

Author

Ohte, Satoshi, primary, Shin, Masashi, additional, Sasanuma, Hiroki, additional, Yoneyama, Katsumi, additional, Akita, Masumi, additional, Ikebuchi, Kenji, additional, Jimi, Eijiro, additional, Maruki, Yuichi, additional, Matsuoka, Masaru, additional, Namba, Akira, additional, Tomoda, Hiroshi, additional, Okazaki, Yasushi, additional, Ohtake, Akira, additional, Oda, Hiromi, additional, Owan, Ichiro, additional, Yoda, Tetsuya, additional, Furuya, Hirokazu, additional, Kamizono, Jyunji, additional, Kitoh, Hiroshi, additional, Nakashima, Yasuharu, additional, Susami, Takafumi, additional, Haga, Nobuhiko, additional, Komori, Tetsuo, additional, and Katagiri, Takenobu, additional

Published
2011
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19. Dual Roles of Smad Proteins in the Conversion from Myoblasts to Osteoblastic Cells by Bone Morphogenetic Proteins

Author

Nojima, Junya, primary, Kanomata, Kazuhiro, additional, Takada, Yumi, additional, Fukuda, Toru, additional, Kokabu, Shoichiro, additional, Ohte, Satoshi, additional, Takada, Takatora, additional, Tsukui, Tohru, additional, Yamamoto, Takamasa S., additional, Sasanuma, Hiroki, additional, Yoneyama, Katsumi, additional, Ueno, Naoto, additional, Okazaki, Yasushi, additional, Kamijo, Ryutaro, additional, Yoda, Tetsuya, additional, and Katagiri, Takenobu, additional

Published
2010
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23. Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3beta-dependent and beta-catenin-independent mechanism.

Author

Fukuda T, Kokabu S, Ohte S, Sasanuma H, Kanomata K, Yoneyama K, Kato H, Akita M, Oda H, and Katagiri T

Subjects
Alkaline Phosphatase metabolism, Animals, Blotting, Western, Bone Morphogenetic Proteins genetics, Cells, Cultured, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 beta, Luciferases metabolism, Mice, Myoblasts cytology, Myoblasts metabolism, Osteoblasts metabolism, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Smad1 Protein genetics, Smad1 Protein metabolism, Bone Morphogenetic Proteins metabolism, Cell Differentiation physiology, Glycogen Synthase Kinase 3 metabolism, Osteoblasts cytology, Wnt Proteins physiology, beta Catenin physiology
Abstract

Both BMPs and Wnts play important roles in the regulation of bone formation. We examined the molecular mechanism regulating cross-talk between BMPs and Wnts in the osteoblastic differentiation of C2C12 cells. Canonical Wnts (Wnt1 and Wnt3a) but not non-canonical Wnts (Wnt5a and Wnt11) synergistically stimulated ALP activity in the presence of BMP-4. Wnt3a and BMP-4 synergistically stimulated the expression of type I collagen and osteonectin. However, Wnt3a did not stimulate ALP activity that was induced by a constitutively active BMP receptor or Smad1. Noggin and Dkk-1 suppressed the synergistic effect of BMP-4 and Wnt3a, but Smad7 did not. Overexpression of beta-catenin did not affect BMP-4-induced ALP activity. By contrast, inhibition or stimulation of GSK3beta activity resulted in either stimulation or suppression of ALP activity, respectively, in the presence of BMP-4. Taken together, these findings suggest that BMPs and canonical Wnts may regulate osteoblastic differentiation, especially at the early stages, through a GSK3beta-dependent but beta-catenin-independent mechanism., (Copyright 2010 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Published
2010
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24. Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production.

Author

Hidano S, Sasanuma H, Ohshima K, Seino K, Kumar L, Hayashi K, Hikida M, Kurosaki T, Taniguchi M, Geha RS, Kitamura D, and Goitsuka R

Subjects
Adaptor Proteins, Signal Transducing genetics, Animals, Carrier Proteins genetics, Mice, Mice, Inbred BALB C, Mice, Transgenic, Phosphoproteins genetics, Signal Transduction immunology, Adaptor Proteins, Signal Transducing immunology, Carrier Proteins immunology, Cytotoxicity, Immunologic, Gene Expression Regulation, Interferon-gamma immunology, Killer Cells, Natural immunology, Phosphoproteins immunology
Abstract

Activation of NK cells is triggered by multiple receptors. We demonstrate here that SLP-76 is required for CD16- and NKG2D-mediated NK cell cytotoxicity, while MIST negatively regulates these responses in an SLP-76-dependent manner. Exceptionally, MIST acts as a positive regulator of cytotoxicity against YAC-1 cells, although SLP-76 plays a more key role. SLP-76 acts as a dominant positive regulator for both NKG2D-mediated and YAC-1 cell-triggered IFN-gamma production. Although NKG2D-mediated IFN-gamma production depends on phospholipase C (PLC) gamma 2, YAC-1 cell-triggered IFN-gamma production is PLC gamma 2- and Syk/ZAP-70 independent and nuclear factor-kappa B mediated. SLP-76 is required for this process in the presence of MIST but is dispensable in the absence of MIST. Thus, YAC-1 cell-triggered NKG2D-independent IFN-gamma production appears to be regulated by SLP-76-dependent and -independent pathways, in which the latter is negatively regulated by MIST. Taken together, these results suggest that SLP-76 and MIST distinctly but interactively regulate NK cell cytotoxicity and IFN-gamma production.

Published
2008
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25. Dual function for the adaptor MIST in IFN-gamma production by NK and CD4+NKT cells regulated by the Src kinase Fgr.

Author

Sasanuma H, Tatsuno A, Hidano S, Ohshima K, Matsuzaki Y, Hayashi K, Lowell CA, Kitamura D, and Goitsuka R

Subjects
Adaptor Proteins, Signal Transducing, Animals, Base Sequence, Carrier Proteins chemistry, Carrier Proteins genetics, DNA, Complementary genetics, Female, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Metastasis physiopathology, Phenotype, Phospholipase C gamma metabolism, Protein Structure, Tertiary, Proto-Oncogene Proteins chemistry, Proto-Oncogene Proteins genetics, Signal Transduction, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, src Homology Domains, src-Family Kinases chemistry, src-Family Kinases genetics, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Carrier Proteins metabolism, Interferon-gamma biosynthesis, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Proto-Oncogene Proteins metabolism, src-Family Kinases metabolism
Abstract

Natural killer (NK) cells and NKT cells play critical early roles in host defense. Here we show that MIST, an adaptor protein belonging to the SLP-76 family, functions negatively in NK cells but positively in CD4(+)NKT cells. NK-cell receptor-mediated IFN-gamma production was enhanced in NK cells, whereas TCR- or NK-cell receptor-mediated cytokine production was reduced in CD4(+)NKT cells from MIST-deficient mice. These opposite effects of MIST paralleled the exclusive expression of the Src family kinase, Fgr, in NK cells between the 2 cell populations. We further demonstrated that interaction of MIST with Fgr, mediated by the C-terminal proline-rich region of MIST and the SH3 domain of Fgr, was required for the suppression of NK-cell receptor-induced IFN-gamma production. This functional interdependence of signaling molecules demonstrates a new mechanism by which adaptor proteins can act as molecular switches to control diverse responses in different cell populations.

Published
2006
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