DERIVATION, PROPAGATION AND GENETIC MODIFICATION OF RAT EMBRYONIC STEM CELLS

描述（由申请方提供）：在生理学和免疫学方面，大鼠与人类的相关性高于小鼠。这项研究的核心假设是，为小鼠开发的基于胚胎干细胞（ES）的技术可以应用于用大鼠ES细胞创建基因靶向大鼠模型。已经建立了健壮的和生殖系感受态的大鼠ES细胞（Cell 135：1299-310，2008. Cell 153：1287-98）。该项目的总体目标是开发用于人类疾病研究的转基因和基因敲除大鼠模型的有效和常规生产方法。为了实现这一目标，我们将：（1）开发方法，以最大限度地提高大鼠ES细胞的生殖系传递效率。(2)优化生殖系感受态大鼠ES细胞稳健增殖的条件。(3)产生基因靶向的大鼠ES细胞和大鼠。 公共卫生相关性：这项研究将有助于利用大鼠ES细胞作为一个平台，通过建立疾病模型来解决与人类疾病相关的基本生物学问题。

DESCRIPTION (provided by applicant): 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.