SPECIAL MOUSE STRAINS RESOURCE

特殊小鼠品系资源

• 批准号: 7153971
• 负责人: MURIEL T DAVISSON
• 金额: $ 53.82万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7153971
• 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

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, and asthma. Even genetically "simple" single mutation diseases are frequently modulated in severity by secondary genes. The advances in positional cloning and 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. We propose to fund with this grant a resource of special mouse strains that are valuable tools for complex trait analysis and whose use will improve the efficiency of identifying genes in mouse models of human multigenic diseases. The Special Mouse Strains Resource (SMSR) will contain six Recombinant Inbred (RI) strain panels, a set of 21 Chromosome Substitution (CSS) strains, and multiple Congenic strains. The RI and congenic strains are already at The Jackson Laboratory but are in need of partial support to continue to maintain them in breeding colonies. The CSS strains will be imported from Dr. J. Nadeau, Case Western Reserve University. To enhance the value of the strains we will 1) increase the number of DNA markers genotyped in the RI strain sets to improve their value for genetic mapping, 2) define more precisely the extent of differential segments in the congenic strains to improve their value for genetic mapping, and 3) phenotype the CSS strains to improve their baseline characterization. We will also develop a database of phenotypic information on the RI, CS, and congenic strains covered by this grant and a graphic map of the distribution and extent of differential segments in the congenic strain set.

许多常见的人类遗传疾病的基因都很复杂；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、肥胖症和哮喘。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。定位克隆和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，用于复杂性状分析的连锁杂交既耗时又昂贵。我们建议用这笔赠款资助特殊小鼠品系的资源，这些品系是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。特殊小鼠品系资源 (SMSR) 将包含 6 个重组近交系 (RI) 品系组、一组 21 条染色体替换 (CSS) 品系和多个同类品系。 RI 和同源菌株已经在杰克逊实验室，但需要部分支持才能继续在繁殖群体中维持它们。 CSS 菌株将从凯斯西储大学的 J. Nadeau 博士进口。为了提高菌株的价值，我们将 1) 增加 RI 菌株组中基因分型的 DNA 标记数量，以提高其遗传作图价值，2) 更精确地定义同源菌株中差异片段的范围，以提高其在遗传图谱分析中的价值。遗传图谱，3) 对 CSS 菌株进行表型分析，以改善其基线特征。我们还将开发一个关于 RI、CS 和本次资助所涵盖的同源菌株的表型信息数据库，以及同源菌株集中差异片段的分布和范围的图表。