MOUSE GENETIC RESOURCES FOR MULTIGENIC DISEASE ANALYSIS: AIDS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。关于艾滋病：描述（由申请人提供）：许多常见的人类疾病模型和许多具有重大生物学意义的特性在实验室小鼠的近亲繁殖品系中存在差异。解剖它们的多基因控制并确定相关基因是出了名的困难。染色体替代菌株（CSSs）是一种具有特定遗传背景的单染色体替代菌株，它代表了一种新的、强大的模式。利用其他来源的资金进行的概念验证研究表明，这些菌株在检测任何其他制图方法无法检测到的遗传变异方面非常强大。在上一个资助期内，我们在B6完成了22间CSSs的建造。A-Chr面板。这些菌株提供给杰克逊实验室保存和分发，作为生物医学研究界的资源。另外，A.B6-Chr CSS 1个，129. chr CSS 8个。B6和B6.129 css已完成，其余面板正在建造中。我们提出了两个具体目标：具体目标一：完成129的建设。B6和B6.129 css。8个品系已经完成，其余的处于回交的不同阶段。这些css可用于解剖这些菌株之间不同性状的遗传控制，它们可用于表征修饰基因，这些修饰基因调节由来自129/Sv小鼠的ES（胚胎干）细胞产生的工程突变小鼠的表型，它们可用于鉴定对建立ES细胞系至关重要的蛋白质。具体目标2：完成10129的建设。MOLF css。这些菌株对于研究这些来自10万多年前分化的小鼠的菌株之间的不同特征将是有价值的。这些菌株也可用于表征调节这些小鼠表型的修饰基因。这些CSS面板将通过促进qtl的检测和发现，彻底改变复杂性状的研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Regarding AIDS: DESCRIPTION (provided by applicant): Many models of common human diseases and numerous traits of great biological interest vary among inbred strains of laboratory mice. Dissecting their multigenic control and identifying the responsible genes has been notoriously difficult. Chromosome substitution strains (CSSs), single chromosome substitutions on a defined and inbred genetic background, represent a novel and powerful paradigm. Proof-of-concept studies, with funds from other sources, demonstrated that these strains are remarkably powerful for detecting genetic variants that eluded detection with any other mapping method. During the previous funding period, we completed construction of the 22 CSSs in the B6.A-Chr panel. These strains were provided to the Jackson Laboratory for preservation and distribution as a resource for the biomedical research community. In addition, one A.B6-Chr CSS, and eight 129.B6 and B6.129 CSSs were completed and the remainder of these panels is under construction. We propose two Specific Aims: Specific Aim 1: Complete construction of the 129.B6 and B6.129 CSSs. Eight strains are complete and the remainder is at various stages of backcrossing. These CSSs can be used to dissect the genetic control of traits that differ between these strains, they can be used to characterize modifier genes that modulate phenotypes of mice with engineered mutations that are made with ES (embryonic stem) cells that are derived from 129/Sv mice, and they can be used to identify proteins that are critical to establish ES cell lines. Specific Aim 2: Complete construction of 10 129.MOLF CSSs. These strains will be valuable for studying traits that differ between these strains that are derived from mice that diverged more than 100,000 years ago. These strains can also be used to characterize modifier genes that modulate phenotypes in these mice. These CSS panels will revolutionize studies of complex traits by facilitating detection and discovery of QTLs.