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组合遗传和信息研究工具，以进一步提高小鼠作为了解人类生物学的模式生物的实用性。这是一组22 C57 BL/6 J-Chr #PWD同源（染色体置换）品系，其中每个品系携带来自C57 BL/6 J（B6）遗传背景上PWD近交品系的单个不同染色体。最近的观察表明，近交系小鼠品系之间的遗传变异主要来自于两个亚种小家鼠（Mus musculus arteriticus）和小家鼠（M. M. musculus的研究表明，将这些亚种之一的染色体渐渗到另一个亚种中将捕获常见菌株中的大多数变异，从而提供“通用的同体组”。在捷克共和国即将完成的一套染色体组菌株接近这一理想，因为PWD的染色体，一个纯的M。M. musculus菌株，正在渗入到B6背景中，B6背景是80%M。M.阿提库斯我们将把这些菌株导入杰克逊实验室，使其广泛可用，并对它们进行一系列生理学上重要的表型表征，并将所得信息存款现有的小鼠表型数据库。表型包括生长和生育力、睡眠障碍、肺功能、肾功能、肥胖症、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。对这一染色体组进行表型分析将立即识别出含有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多种小鼠模型，可用于进一步探索复杂疾病和表型的遗传基础。后基因组时代的基因型和表型之间的联系将需要大规模、全系统的方法和基础设施。我们认为，这些具有许多表型特征的consomic小鼠的可用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.