Special Mouse Strains Resource

描述（由申请人提供）：许多常见和普遍的人类疾病在遗传上是复杂的;也就是说，它们是由多种遗传、发育和环境因素相互作用引起的。即使是单基因突变疾病，也经常通过修饰基因来调节发病、严重程度和进展。这个项目的长期目标，特殊小鼠品系资源（SMSR），是维护，分发，并提供信息的遗传工具，用于分析复杂的性状。SMSR中的资源目前包括小鼠的六个重组近交（RI）和两个染色体置换（CS）品系组，其是提高在人多基因疾病的小鼠模型中鉴定基因的效率的有价值的工具。这些小鼠品系的集合为具有累积基因分型的表型分型提供了永久资源。本申请中的一个主要的新举措是建议通过开发一组来自个体菌株的生殖系感受态胚胎干细胞系来增强C57 BL/6 J-Chr #A/NaJ染色体置换（同源）组的能力，所述生殖系感受态胚胎干细胞系用于测试共等基因菌株背景中的候选基因、细胞表型和数量性状的体外建模。该资助的具体目的是：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者; 2）通过制备和分发C57 BL/6 J-Chr #A/NaJ consomic品系的ES细胞系来提高SMSR品系的价值;和3）提供科学界容易获得的SMSR菌株的完整和准确的信息。在小鼠模型中识别负责复杂疾病的基因通常可以预测人类疾病基因的位置，基于小鼠和人类基因组的保守区域;因此，这些资源显着有助于解决人类复杂遗传疾病。

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.