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.
This study will facilitate the use of rat ES cells as a platform to address fundamental biological questions related to human disease through the creation of disease models.
| 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 |
| 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 |
| Huang, Guanyi; Ashton, Charles; Kumbhani, Dhruv S et al. (2011) Genetic manipulations in the rat: progress and prospects. Curr Opin Nephrol Hypertens 20:391-9 |
| Tong, Chang; Huang, Guanyi; Ashton, Charles et al. (2011) Generating gene knockout rats by homologous recombination in embryonic stem cells. Nat Protoc 6:827-44 |
| Tong, Chang; Li, Ping; Wu, Nancy L et al. (2010) Production of p53 gene knockout rats by homologous recombination in embryonic stem cells. Nature 467:211-3 |
