Special Mouse Strains Resource

描述（由申请人提供）：许多常见的遗传性人类疾病在基因上是复杂的；也就是说，它们是多个基因相互作用的结果。例如糖尿病、心血管疾病、癌症、肥胖、哮喘和对传染病的易感性。即使是遗传上“简单”的单突变疾病，其严重程度也经常受到次级基因的调节。定位候选基因分析的进展使得相对快速地鉴定出许多由单基因突变引起的人类和小鼠疾病的基因。同样，遗传复杂疾病的遗传分析的目标是发现潜在的基因，最终目的是预防或治疗。复杂性状的遗传分析需要能够进行遗传操作的模型系统。小鼠与人类之间的代谢、器官/组织和遗传相似性，以及小鼠易于进行基因操作，使小鼠成为许多这些复杂人类疾病的明显模型。然而，用于复杂性状分析的连锁杂交既耗时又昂贵，因为需要大量的小鼠。由该基金资助的特殊小鼠菌株资源（SMSR）维护和分发菌株面板，这些面板是高效复杂性状分析的宝贵工具，其使用将提高人类多基因疾病小鼠模型中基因识别的效率。SMSR包含5个重组自交系（Rl）菌株面板和21个染色体替换（CS）菌株，共110个个体菌株。我们建议在这次修订的更新中增加第二个CS面板- C57BL/6J-Chr #PWD - 26个菌株和46个额外的BXD Rl菌株。

DESCRIPTION (provided by applicant): Many common inherited human diseases are genetically complex; that is, they result from the interaction of more than one gene. Examples are diabetes, cardiovascular diseases, cancer, obesity, asthma, and susceptibility to infectious disease. Even genetically "simple" single mutation diseases are frequently modulated in severity by secondary genes. The advances in positional candidate gene analysis have led to relatively rapid identification of the genes underlying many human and mouse disorders caused by single gene mutations. Similarly, the goal of genetic analysis of genetically complex diseases is to discover the underlying genes with the ultimate goal of prevention or therapy. Genetic analysis of complex traits requires model systems in which genetic manipulations can be carried out. The metabolic, organ/tissue, and genetic similarities between mice and humans and the ease with which the mouse can be genetically manipulated make mice the obvious model for many of these complex human diseases. Linkage crosses for complex trait analysis, however, are time-consuming and expensive because of the large number of mice required. The Special Mouse Strains Resource (SMSR) funded by this grant maintains and distributes strain panels that are valuable tools for efficient complex trait analysis and whose use will improve the efficiency of identifying genes in mouse models of human polygenic diseases. The SMSR contains five Recombinant Inbred (Rl) strain panels and a set of 21 Consomic or Chromosome Substitution (CS) strains totaling 110 individual strains. We propose in this amended renewal to add a second CS panel - C57BL/6J-Chr #PWD - of 26 strains and 46 additional BXD Rl strains. The specific aims of this grant are to (1) maintain and distribute the existing s110 strains, including develop a panel of SNPs for genetic monitoring of all SMSR strains; (2) add two new strains sets (above);(3) carry out research to enhance the value of the strains - (a) characterize selected phenotypes, including immunology, hematology, clinical chemistry, lung function, bone density, body composition, behavior, hearing and vision, and (b) collect reproductive data on all strains maintained; and (4) provide all data generated to the scientific public via the Mouse Phenome Database and the JAX web site. Because mice and human beings get the same genetically complex diseases, identifying the genetic basis for these complex diseases in mice will lead to preventive and therapeutic treatments in human patients for diseases such as heart disease, diabetes, obesity, asthma, and susceptibility to infectious diseases.