Rats are more relevant to humans than mice, both physiologically and pharmacologically. The central HYPOTHESIS behind the proposed research is that embryonic stem (ES) cell- based technologies developed for the mouse can be applied to create gene targeted rat models with rat ES cells. Robust and germline competent rat ES cells have been established (Cell 135:1299-310, 2008. Cell 153:1287-98). The overall GOAL of this project is to develop methods for the efficient and routine production of transgenic and gene knock- out rat models for the study of human disease. To achieve this goal, we will: (1) Develop methods to maximize germline transmission efficiency of rat ES cells. (2) Optimize conditions for robust propagation of germline competent rat ES cells. (3) Produce gene targeted rat ES cells and rats.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Research Project (R01)
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Development - 2 Study Section (DEV2)
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Mirochnitchenko, Oleg
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University of Southern California
Anatomy/Cell Biology
Schools of Medicine
Los Angeles
United States
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Chen, Xi; Ye, Shoudong; Ying, Qi-Long (2015) Stem cell maintenance by manipulating signaling pathways: past, current and future. BMB Rep 48:668-76
Huang, Guanyi; Ye, Shoudong; Zhou, Xingliang et al. (2015) Molecular basis of embryonic stem cell self-renewal: from signaling pathways to pluripotency network. Cell Mol Life Sci 72:1741-57
Ye, Shoudong; Liu, Dahai; Ying, Qi-Long (2014) Signaling pathways in induced naïve pluripotency. Curr Opin Genet Dev 28:10-5
Yan, H-X; Wu, H-P; Zhang, H-L et al. (2013) DNA damage-induced sustained p53 activation contributes to inflammation-associated hepatocarcinogenesis in rats. Oncogene 32:4565-71
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Yan, He-Xin; Wu, Hong-Ping; Zhang, Hui-Lu et al. (2013) p53 promotes inflammation-associated hepatocarcinogenesis by inducing HMGB1 release. J Hepatol 59:762-8
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Yan, He-Xin; Wu, Hong-Ping; Ashton, Charles et al. (2012) Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis. Carcinogenesis 33:2001-5
Huang, Guanyi; Tong, Chang; Kumbhani, Dhruv S et al. (2011) Beyond knockout rats: new insights into finer genome manipulation in rats. Cell Cycle 10:1059-66

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