Mouse Core

Mouse Core旨在为项目研究项目和核心提供动物育种、维护和表型鉴定资源，重点关注WRN基因、基因组不稳定性和肿瘤发生。这一核心以提高动物使用效率的方式解决了方案项目的动物需求。两个共同的主题是流行的：1)基因改变小鼠的产生和使用，以及2)使用整体动物分析来帮助表征肿瘤发展的特征和其他相关的表型。特定目标1将产生新的ES细胞和WRN错义突变的“敲入”小鼠模型，并确定它们的细胞和组织表型。这个核心将提供转基因技术、资源和专业知识，以产生新的小鼠品系。所有的资源都已经到位，可以让 靶向载体，靶向小鼠ES细胞，产生嵌合体和突变小鼠，并对后代进行基因分型，以确定永久创始人。特殊目标2将维持新的和已建立的小鼠品系的繁育群体。使用合理的育种方法和准确的记录保存，在几代回交过程中保持特定品系的遗传变化的完整性是至关重要的。此外，还将在群体层面进行基本的观察评估，以发现新产生的小鼠品系的任何不寻常特征。特定目标3将对基因定义的小鼠的实验队列进行纵向研究。将监测和评估参与项目实验的小鼠的表型变化。需要一种系统的方法来检测表型差异，这种差异不容易通过 不经意的观察。这个核心将提供老鼠成像资源，作为表型鉴定程序的一部分。对动物核心的需求是最重要的，因为所有的项目都使用老鼠。整合专注于最大化效率和最小化成本的动物资源是该计划项目成功的关键。

The Mouse Core is designed to provide animal breeding, maintenance, and phenotyping resources for program research projects and cores with a focus on the WRN gene, genomic instability and tumorigenesis. This core addresses the animal needs of the program project in a way as to increase the efficiency of animal use. Two common themes are prevalent: 1) the generation and use of genetically altered mice, and 2) the use of whole animal assays to help characterize features of tumor development and other related phenotypes. Specific aim 1 will generate new ES cell and 'knock-in' mouse models of WRN missense mutations and determine their cellular and organismal phenotypes. This core will provide the transgenic technology, resources and expertise to generate new lines of mice. All of the resources are in place to make targeting vectors, target mouse ES cells, generate chimeras and mutant mice, and genotype offspring to identify permanent founders. Specific aim 2 will maintain breeding colonies for new and established lines of mice. It is essential that the integrity of the genetic alteration of a specific line be maintained over several generations of back-crossing using sound breeding practices and accurate record keeping. In addition, basic observational assessments will be performed at the colony level to detect any unusual characteristics of newly generated mouse lines. Specific Aim 3 will conduct longitudinal studies on experimental cohorts of genetically defined mice. Phenotypic changes will be monitored and assessed in mice involved in project experiments. A systematic approach is necessary to detect phenotypic differences not easily discernible by casual observations. This core will provide mouse imaging resources as part of the phenotyping procedure. The need for an animal core is paramount in that all projects use mice. Consolidation of animal resources focused on maximizing efficiency and minimizing costs is essential to the success of this program project.