10 results on '"Willis, Brandon J"'
Search Results
2. Whole genome analysis for 163 gRNAs in Cas9-edited mice reveals minimal off-target activity
- Author
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Peterson, Kevin A., Khalouei, Sam, Hanafi, Nour, Wood, Joshua A., Lanza, Denise G., Lintott, Lauri G., Willis, Brandon J., Seavitt, John R., Braun, Robert E., Dickinson, Mary E., White, Jacqueline K., Lloyd, K. C. Kent, Heaney, Jason D., Murray, Stephen A., Ramani, Arun, and Nutter, Lauryl M. J.
- Published
- 2023
- Full Text
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3. Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation
- Author
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Gurumurthy, Channabasavaiah B., O’Brien, Aidan R., Quadros, Rolen M., Adams, Jr, John, Alcaide, Pilar, Ayabe, Shinya, Ballard, Johnathan, Batra, Surinder K., Beauchamp, Marie-Claude, Becker, Kathleen A., Bernas, Guillaume, Brough, David, Carrillo-Salinas, Francisco, Chan, Wesley, Chen, Hanying, Dawson, Ruby, DeMambro, Victoria, D’Hont, Jinke, Dibb, Katharine M., Eudy, James D., Gan, Lin, Gao, Jing, Gonzales, Amy, Guntur, Anyonya R., Guo, Huiping, Harms, Donald W., Harrington, Anne, Hentges, Kathryn E., Humphreys, Neil, Imai, Shiho, Ishii, Hideshi, Iwama, Mizuho, Jonasch, Eric, Karolak, Michelle, Keavney, Bernard, Khin, Nay-Chi, Konno, Masamitsu, Kotani, Yuko, Kunihiro, Yayoi, Lakshmanan, Imayavaramban, Larochelle, Catherine, Lawrence, Catherine B., Li, Lin, Lindner, Volkhard, Liu, Xian-De, Lopez-Castejon, Gloria, Loudon, Andrew, Lowe, Jenna, Jerome-Majewska, Loydie A., Matsusaka, Taiji, Miura, Hiromi, Miyasaka, Yoshiki, Morpurgo, Benjamin, Motyl, Katherine, Nabeshima, Yo-ichi, Nakade, Koji, Nakashiba, Toshiaki, Nakashima, Kenichi, Obata, Yuichi, Ogiwara, Sanae, Ouellet, Mariette, Oxburgh, Leif, Piltz, Sandra, Pinz, Ilka, Ponnusamy, Moorthy P., Ray, David, Redder, Ronald J., Rosen, Clifford J., Ross, Nikki, Ruhe, Mark T., Ryzhova, Larisa, Salvador, Ane M., Alam, Sabrina Shameen, Sedlacek, Radislav, Sharma, Karan, Smith, Chad, Staes, Katrien, Starrs, Lora, Sugiyama, Fumihiro, Takahashi, Satoru, Tanaka, Tomohiro, Trafford, Andrew W., Uno, Yoshihiro, Vanhoutte, Leen, Vanrockeghem, Frederique, Willis, Brandon J., Wright, Christian S., Yamauchi, Yuko, Yi, Xin, Yoshimi, Kazuto, Zhang, Xuesong, Zhang, Yu, Ohtsuka, Masato, Das, Satyabrata, Garry, Daniel J., Hochepied, Tino, Thomas, Paul, Parker-Thornburg, Jan, Adamson, Antony D., Yoshiki, Atsushi, Schmouth, Jean-Francois, Golovko, Andrei, Thompson, William R., Lloyd, K. C. Kent, Wood, Joshua A., Cowan, Mitra, Mashimo, Tomoji, Mizuno, Seiya, Zhu, Hao, Kasparek, Petr, Liaw, Lucy, Miano, Joseph M., and Burgio, Gaetan
- Published
- 2019
- Full Text
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4. Rescue of germline transmission from chimeras by IVF after sperm analysis
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Li, Ming-Wen, Willis, Brandon J., Evans, Kristin D., Araiza, Renee S., Lee, Angus Yiu-Fai, and Lloyd, K. C. Kent
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- 2015
- Full Text
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5. Assessment of three generations of mice derived by ICSI using freeze-dried sperm
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Li, Ming-Wen, Willis, Brandon J., Griffey, Stephen M., Spearow, Jimmy L., and Kent Lloyd, K. C.
- Published
- 2009
6. On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.
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Blackburn, Michael L., Wankhade, Umesh D., Ono-Moore, Kikumi D., Chintapalli, Sree V., Fox, Renee, Rutkowsky, Jennifer M., Willis, Brandon J., Tolentino, Todd, Lloyd, K. C. Kent, and Adams, Sean H.
- Subjects
BROWN adipose tissue ,GLOBIN ,MYOGLOBIN ,KNOCKOUT mice ,CONCEPTUAL models ,CYTOCHROME oxidase ,UNCOUPLING proteins - Abstract
Myoglobin (Mb) regulates O
2 bioavailability in muscle and heart as the partial pressure of O2 (PO2 ) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher PO2 and converting NO2 - to NO as PO2 falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but its function is unknown. Herein, we present a new conceptual model that proposes links between BAT thermogenic activation, concurrently reduced PO2 , and NO pools regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We describe the effect of Mb knockout (Mb-/- ) on BAT phenotype [lipid droplets, mitochondrial markers uncoupling protein 1 (UCP1) and cytochrome C oxidase 4 (Cox4), transcriptomics] in male and female mice fed a high-fat diet (HFD, 45% of energy, ~13 wk), and examine Mb expression during brown adipocyte differentiation. Interscapular BAT weights did not differ by genotype, but there was a higher prevalence of mid-large sized droplets in Mb-/- . COX4 protein expression was significantly reduced in Mb-/- BAT, and a suite of metabolic/NO/stress/hypoxia transcripts were lower. All of these Mb-/- -associated differences were most apparent in females. The new conceptual model, and results derived from Mb-/- mice, suggest a role for Mb in BAT metabolic regulation, in part through sexually dimorphic systems and NO signaling. This possibility requires further validation in light of significant mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wild-type mice and lower expression relative to muscle and heart. [ABSTRACT FROM AUTHOR]- Published
- 2021
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7. Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.
- Author
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Ono-Moore, Kikumi D., Olfert, I. Mark, Rutkowsky, Jennifer M., Chintapalli, Sree V., Willis, Brandon J., Blackburn, Michael L., Williams, D. Keith, O'Reilly, Juliana, Tolentino, Todd, Lloyd, K. C. Kent, and Adams, Sean H.
- Subjects
SKELETAL muscle physiology ,MYOGLOBIN ,KNOCKOUT mice ,WEIGHT gain ,INSULIN sensitivity ,HOMEOSTASIS - Abstract
Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart, at least when tissue O2 levels drop. Mb also plays a role in regulating cellular nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggest additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance, and insulin sensitivity in Mb knockout (Mb
-/- ) and wild-type (WT) mice challenged with a high-fat diet (HFD, 45% of calories). In males (n = 10/genotype) and females (n = 9/genotype) tested at 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10°C, 72 h), and glucose and insulin tolerance, were not different compared with within-sex WT controls. At ~18 and ~19 wk of age, female Mb-/- adiposity was ~42%-48% higher versus WT females (P = 0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb-/- , specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency. [ABSTRACT FROM AUTHOR]- Published
- 2021
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8. Generation of desminopathy in rats using CRISPR‐Cas9.
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Langer, Henning T., Mossakowski, Agata A., Willis, Brandon J., Grimsrud, Kristin N., Wood, Joshua A., Lloyd, Kevin C.K., Zbinden‐Foncea, Hermann, and Baar, Keith
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CYTOSKELETAL proteins ,MUSCLE diseases ,ANIMALS ,HUMAN phenotype ,DISEASE progression ,RATS - Abstract
Background: Desminopathy is a clinically heterogeneous muscle disease caused by over 60 different mutations in desmin. The most common mutation with a clinical phenotype in humans is an exchange of arginine to proline at position 350 of desmin leading to p.R350P. We created the first CRISPR‐Cas9 engineered rat model for a muscle disease by mirroring the R350P mutation in humans. Methods: Using CRISPR‐Cas9 technology, Des c.1045‐1046 (AGG > CCG) was introduced into exon 6 of the rat genome causing p.R349P. The genotype of each animal was confirmed via quantitative PCR. Six male rats with a mutation in desmin (n = 6) between the age of 120–150 days and an equal number of wild type littermates (n = 6) were used for experiments. Maximal plantar flexion force was measured in vivo and combined with the collection of muscle weights, immunoblotting, and histological analysis. In addition to the baseline phenotyping, we performed a synergist ablation study in the same animals. Results: We found a difference in the number of central nuclei between desmin mutants (1 ± 0.4%) and wild type littermates (0.2 ± 0.1%; P < 0.05). While muscle weights did not differ, we found the levels of many structural proteins to be altered in mutant animals. Dystrophin and syntrophin were increased 54% and 45% in desmin mutants, respectively (P < 0.05). Dysferlin and Annexin A2, proteins associated with membrane repair, were increased two‐fold and 32%, respectively, in mutants (P < 0.05). Synergist ablation caused similar increases in muscle weight between mutant and wild type animals, but changes in fibre diameter revealed that fibre hypertrophy in desmin mutants was hampered compared with wild type animals (P < 0.05). Conclusions: We created a novel animal model for desminopathy that will be a useful tool in furthering our understanding of the disease. While mutant animals at an age corresponding to a preclinical age in humans show no macroscopic differences, microscopic and molecular changes are already present. Future studies should aim to further decipher those biological changes that precede the clinical progression of disease and test therapeutic approaches to delay disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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9. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.
- Author
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Chen, Jane Q., Mori, Hidetoshi, Cardiff, Robert D., Trott, Josephine F., Hovey, Russell C., Hubbard, Neil E., Engelberg, Jesse A., Tepper, Clifford G., Willis, Brandon J., Khan, Imran H., Ravindran, Resmi K., Chan, Szeman R., Schreiber, Robert D., and Borowsky, Alexander D.
- Subjects
MAMMARY glands ,STROMAL cells ,LABORATORY mice ,ESTROGEN receptors ,MORPHOGENESIS - Abstract
Female 129:Stat1-null mice (129S6/SvEvTac-Stat1
tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
10. Assessment of three generations of mice derived by ICSI using freeze-dried sperm.
- Author
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Ming-Wen Li, Willis, Brandon J., Griffey, Stephen M., Spearow, Jimmy L., and Lloyd, K. C. Kent
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FERTILIZATION in vitro ,SPERMATOZOA ,REPRODUCTIVE technology ,BLASTOCYST ,OVUM ,EMBRYOLOGY ,MICE - Abstract
Although the derivation of mice by intracytoplasmic sperm injection (ICSI) using freeze-dried sperm has been demonstrated previously, a comprehensive analysis of their viability, health, and fertility has not. The purpose of the present study was to determine the extent to which ICSI using freeze-dried sperm stored at 4 ?C for 1-2 months from mice on either an inbred (C57BL/6J) or hybrid (B6D2F1/J) genetic background results in genomic instability and/or phenotypic abnormality in mice and two generations of their progeny. Fertilization rates (number of 2-cells per injected oocytes) using ICSI of fresh and freezedried sperm were similar within and between mouse strains, although fewer freeze-dried sperm-derived embryos than fresh sperm-derived embryos developed to blastocysts in vitro (C57BL/6J and B6D2F1/J) and live born pups in vivo (B6D2F1/J only). Nevertheless, once born, mice derived by ICSI using freezedried sperm in both mouse strains were healthy and reproductively sound. No major differences in litter size, weaning rate, and sex ratio were noted in the two generations of progeny (F2 and F3) of ICSI-derived offspring using freeze-dried sperm compared with that in the natural mating (control) group. Further, there was no evidence that either ICSI or freeze drying induced genomic instability, as determined by microsatellite analysis of the derived mice and subsequent generations when compared with both parental genotypes, nor were there differences in the number or types of pathological changes in any of the three generations of progeny. We conclude that viable, healthy and genomically stable mice can be derived by ICSI using freeze-dried mouse sperm stored in the refrigerator for at least 2 months. Further, because freeze drying is a simpler and more economical technique compared with embryo and sperm cryopreservation, the results of this study justify additional research to continue to develop and enhance the technique for the preservation, storage, and sharing of genetically altered mice. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
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