DERIVATION, PROPAGATION AND GENETIC MODIFICATION OF RAT EMBRYONIC STEM CELLS

描述（由申请人提供）：在生理和药理学上，大鼠与人类的关系比小鼠更密切。这项研究的核心假设是，为小鼠开发的基于胚胎干细胞的技术可以应用于用大鼠胚胎干细胞创建基因靶向大鼠模型。大鼠胚胎干细胞已经建立（Cell 135:1299- 310,2008）。细胞153:1287 - 98)。该项目的总体目标是开发高效和常规生产转基因和基因敲除大鼠模型的方法，用于研究人类疾病。为了实现这一目标，我们将：(1)开发最大化大鼠胚胎干细胞种系传递效率的方法。(2)优化大鼠种系胚胎干细胞稳健繁殖的条件。(3)制备基因靶向大鼠ES细胞和大鼠。

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.