Abstract

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.

Public Health Relevance

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Research Project (R01)
Project #
5R01OD010926-04
Application #
8435437
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Mirochnitchenko, Oleg
Project Start
2010-01-01
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$382,480
Indirect Cost
$146,381

  Institution

Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

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
Xi, Guangjun; Hu, Pingfang; Qu, Cunye et al. (2013) Induced neural stem cells generated from rat fibroblasts. Genomics Proteomics Bioinformatics 11:312-9
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
Hong, James; He, Hong; Bui, Phuoc et al. (2013) A focused microarray for screening rat embryonic stem cell lines. Stem Cells Dev 22:431-43
Tong, Chang; Huang, Guanyi; Ashton, Charles et al. (2012) Rapid and cost-effective gene targeting in rat embryonic stem cells by TALENs. J Genet Genomics 39:275-80
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
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

Showing the most recent 10 out of 13 publications