Special Mouse Strains Resource

描述（由申请人提供）：许多常见和普遍的人类疾病是遗传复杂的；也就是说，它们是多种遗传、发育和环境因素相互作用的结果。即使是单基因突变疾病，其发病、严重程度和进展也经常受到修饰基因的调节。该项目的长期目标是维护、分发和提供用于分析复杂性状的遗传工具的信息。SMSR的资源目前包括6个重组近交系（Rl）和2个染色体替代（CS）小鼠品系，它们是提高人类多基因疾病小鼠模型中基因鉴定效率的宝贵工具。这些小鼠品系为累积基因分型提供了永久的表型资源。该应用程序的一个主要新倡议是建议通过从单个菌株中开发一组生殖系胜任的胚胎干细胞系来增强C57BL/6J- Chr#A/NaJ染色体替代（consomic）集的功能，用于共等基因菌株背景下的候选基因测试，细胞表型分析和体外定量性状建模。该拨款的具体目的是：1)维持目前包括在SMSR中的小鼠品系作为活菌落，并将这些小鼠分发给研究人员；2)通过为C57BL/6J-Chr#A/NaJ经济型菌株制作和分配ES细胞株，提高SMSR菌株的价值；3)为科学界提供完整、准确、易于获取的SMSR菌株信息。基于小鼠和人类基因组的保守区域，在小鼠模型中鉴定导致复杂疾病的基因往往可以预测人类疾病基因的位置；因此，这些资源显著有助于解决人类复杂的遗传疾病。

DESCRIPTION (provided by applicant): Many common and pervasive human diseases are genetically complex; that is, they result from the interaction of multiple genetic, developmental, and environmental factors. Even single gene mutation diseases are frequently modulated in onset, severity, and progression by modifier genes. The long-term objective of this project, the Special Mouse Strains Resource (SMSR), is to maintain, distribute, and provide information for genetic tools for analyzing complex traits. The resources in the SMSR currently include six Recombinant Inbred (Rl) and two Chromosomal Substitution (CS) strain sets of mice that are valuable tools to improve the efficiency of identifying genes in mouse models of human multigenic diseases. These sets of mouse strains provide a perpetual resource for phenotyping with cumulative genotyping. A major new initiative in this application is a proposal to enhance the power of the C57BL/6J- Chr#A/NaJ Chromosomal Substitution (consomic) set by developing a set of germ line competent, embryonic stem cell lines from the individual strains to be used for testing candidate genes in co-isogenic strain backgrounds, cellular phenotyping, and in-vitro modeling of quantitative traits. The Specific Aims of the grant are to: 1) maintain strains of mice currently included in the SMSR as live colonies and to distribute these mice to investigators; 2) enhance the value of the SMSR strains by making, and distributing, ES cell lines for each of the C57BL/6J-Chr#A/NaJ consomic strains; and 3) provide complete and accurate information for SMSR strains that is easily accessible to the scientific community. Identification of genes responsible for complex diseases in mouse models often predicts the location of human disease genes, based on the conserved regions of mouse and human genomes; consequently, these resources significantly contribute to the resolution of complex genetic diseases in humans.