Consomic Strains Between C57BL/6 and PWD

描述(由申请人提供)：我们建议开发一种新的和强大的遗传和信息研究相结合的工具，以进一步提高小鼠作为理解人类生物学的模式生物的效用。这是一组22C57BL/6J-Chr#PWD共体(染色体替代)品系，每个品系携带一条与PwD近交系不同的染色体，其遗传背景为C57BL/6J(B6)。最近的观察表明，近交系小鼠之间的大部分遗传差异来自两个亚种--小鼠肌肉和肌肉小鼠，这表明将其中一个亚种的染色体导入另一个亚种将捕捉到普通品系之间的大部分变异，提供了一套共同的共生组学。捷克共和国即将完成的一组共生体品系接近于这一理想，因为PWD是一种纯粹的肌肉分枝杆菌品系，其染色体正在导入到B6背景中，这是80%的国内分枝杆菌。我们将把这些菌株输入杰克逊实验室，使它们广泛可用，并对它们进行一系列重要生理表型的表征，并将结果信息存储在现有的小鼠表型数据库中。表型包括生长和生育、睡眠障碍、肺功能、肾功能、肥胖、糖尿病、动脉粥样硬化、胆结石、血液学、骨质疏松症、神经功能、免疫功能、听力、视力、学习、记忆和衰老。对这个共体组进行表型分析，将立即识别出包含影响生物医学感兴趣的特定性状的基因的染色体。这些数据和这组小鼠将为科学界提供各种小鼠模型，可以用来进一步探索复杂疾病和表型的遗传基础。将基因型和表型联系起来的后基因组挑战将需要广泛的、系统范围的方法和基础设施。我们认为，这些具有多种表型特征的群体小鼠的可获得性将有助于应对这一挑战。

DESCRIPTION (provided by applicant): We propose to develop a new and powerful combined genetic and information research tool to further enhance the utility of the mouse as a model organism for understanding human biology. This is a set of 22C57BL/6J-Chr#PWD consomic (chromosome substitution) strains, in which each strain carries a single different chromosome from the PWD inbred strain on a C57BL/6J (B6) genetic background. Recent observations indicate that much of the genetic variation among inbred mouse strains derives from the contributions of the two subspecies Mus musculus domesticus and M. m. musculus suggesting that introgressing the chromosomes of one of these subspecies into the other would capture most variation among common strains, providing a "universal set of consomics". The set of consomic strains that is nearing completion in the Czech Republic comes close to this ideal because the chromosomes of PWD, a pure M. m. musculus strain, are being introgressed into the B6 background, which is 80% M. m. domesticus. We will import these strains into The Jackson Laboratory, make them widely available, and characterize them for a range of physiologically important phenotypes and deposit the resulting information in the existing Mouse Phenome Database. The phenotypes include growth and fertility, sleep disorders, lung function, kidney function, obesity, diabetes, atherosclerosis, gallstones, hematology, osteoporosis, neurological function, immunologic function, hearing, sight, learning, memory, and aging. Phenotyping this consomic set will immediately identify chromosomes that contain genes affecting specific traits of biomedical interest. These data and this set of mice will provide a variety of mouse models to the scientific community that can be used to further explore the genetic basis of complex diseases and phenotypes. The post-genomic challenge of linking genotype and phenotype will require broad-scale, systems-wide approaches and infrastructure. We suggest that the availability of these consomic mice characterized for many phenotypes will help to meet that challenge.