Special Mouse Strains Resource

特殊小鼠品系资源

• 批准号: 7129993
• 负责人: LEAH RAE B DONAHUE
• 金额: $ 66.24万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7129993
• 关键词: animal breeding; autosomal dominant trait; autosomal recessive trait; disease /disorder model; genetic disorder; genetic mapping; genetic markers; genetic registry /resource /referral center; genetic strain; genome; genotype; information dissemination; laboratory mouse; nucleic acid quantitation /detection; phenotype; polymerase chain reaction; quantitative trait loci

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.

描述（由申请人提供）：许多常见的人类遗传疾病在遗传上都很复杂；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、哮喘和传染病易感性。即使是遗传上“简单”的单突变疾病也经常受到二级基因的严重程度调节。位置候选基因分析的进步使得能够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，复杂遗传疾病的基因分析的目标是发现潜在的基因，最终达到预防或治疗的目的。复杂性状的遗传分析需要可以进行遗传操作的模型系统。小鼠和人类之间的代谢、器官/组织和遗传相似性以及小鼠可以轻松地进行基因操纵，使得小鼠成为许多这些复杂的人类疾病的明显模型。然而，由于需要大量小鼠，用于复杂性状分析的连锁杂交既耗时又昂贵。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复杂性状分析的宝贵工具，其使用将提高识别人类多基因疾病小鼠模型中基因的效率。 SMSR 包含五个重组近交系 (R1) 菌株组和一组 21 个康体或染色体替代 (CS) 菌株，总共 110 个单独菌株。我们建议在此修订更新中添加第二个 CS 组 - C57BL/6J-Chr #PWD - 包含 26 个菌株和 46 个额外的 BXD R1 菌株。 这笔赠款的具体目的是（1）维护和分发现有的 s110 菌株，包括开发一组 SNP，用于所有 SMSR 菌株的遗传监测； (2) 增加两个新菌株组（上图）；(3) 开展研究以增强菌株的价值 - (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) 收集所有维持品系的繁殖数据； (4) 通过小鼠表型组数据库和 JAX 网站向科学公众提供生成的所有数据。 由于小鼠和人类患有相同的复杂遗传疾病，因此确定小鼠这些复杂疾病的遗传基础将有助于对人类患者进行预防和治疗，例如心脏病、糖尿病、肥胖、哮喘和易患传染病等疾病。