Special Mouse Strains Resource

描述(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，它们是由多个基因相互作用的结果。例如糖尿病、心血管疾病、癌症、肥胖症、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，其严重程度也常常受到次级基因的影响。位置候选基因分析的进展导致相对快速地确定了由单基因突变引起的许多人类和小鼠疾病的潜在基因。同样，基因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模型系统，在模型系统中可以进行遗传操作。小鼠和人类之间的代谢、器官/组织和遗传相似之处，以及小鼠可以很容易地被基因操纵，使小鼠成为许多这些复杂的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。由这笔赠款资助的特殊小鼠品系资源(SMSR)维护和分发品系面板，这些品系面板是有效的复杂性状分析的宝贵工具，其使用将提高在人类多基因疾病小鼠模型中识别基因的效率。SMSR包含5个重组近交系(RL)品系面板和一组21个共生或染色体替代(CS)品系，总计110个单独品系。在这次修订的更新中，我们建议增加第二个CS面板-C57BL/6J-Chr#PWD-由26个菌株和46个额外的BXD RL菌株组成。 这笔拨款的具体目的是(1)维护和分发现有的S110菌株，包括开发一组用于对所有SMSR菌株进行遗传监测的SNPs；(2)增加两个新的菌株集(上)；(3)开展研究，以提高菌株的价值-(A)表征选定的表型，包括免疫学、血液学、临床化学、肺功能、骨密度、身体成分、行为、听力和视力，以及(B)收集关于维护的所有菌株的生殖数据；以及(4)通过小鼠基因组数据库和JAX网站向科学公众提供所有数据。 由于小鼠和人类患有相同的基因复杂疾病，在小鼠身上识别这些复杂疾病的遗传基础将导致人类患者对心脏病、糖尿病、肥胖症、哮喘和传染病易感性等疾病的预防和治疗。

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.