DERIVATION, PROPAGATION AND GENETIC MODIFICATION OF RAT EMBRYONIC STEM CELLS

描述(申请人提供)：无论在生理上还是药理上，大鼠都比小鼠更接近人类。这项拟议研究背后的中心假设是，为小鼠开发的基于胚胎干细胞的技术可以应用于创建具有大鼠胚胎干细胞的基因靶向大鼠模型。已经建立了健壮的、有生殖系能力的大鼠胚胎干细胞(Cell 135：1299-310,2008)。单元153：1287-98)。该项目的总体目标是开发有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生殖系传递效率的方法。(2)优化繁殖条件，使生殖系感受态大鼠ES细胞健康繁殖。(3)制备基因靶向的大鼠胚胎干细胞和大鼠。 公共卫生相关性：这项研究将促进利用大鼠胚胎干细胞作为平台，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.