MOUSE GENETIC RESOURCES FOR MULTIGENIC DISEASE ANALYSIS: AIDS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。关于艾滋病：描述（由申请人提供）：在实验室小鼠的近交系中，常见人类疾病的许多模型和具有重大生物学意义的许多性状各不相同。剖析它们的多基因控制和识别负责基因是出了名的困难。染色体替代株系（CSSs）是在确定的近交遗传背景上发生的单染色体替代，代表了一种新颖而强大的范例。利用其他来源的资金进行的概念验证研究表明，这些菌株对于检测任何其他作图方法都无法检测到的遗传变异非常强大。在上一个资助期间，我们完成了B6.A-Chr面板中22个CSS的建设。这些菌株被提供给杰克逊实验室作为生物医学研究界的资源进行保存和分配。此外，一个A.B6-Chr CSS和八个129.B6和B6.129 CSS已经完成，其余的这些面板正在建造中。 我们提出了两个具体目标：具体目标1：完成129.B6和B6.129 CSS的构建。八个品系是完整的，其余的处于不同的回交阶段。这些CSS可用于剖析这些品系之间不同的性状的遗传控制，它们可用于表征调节具有工程突变的小鼠表型的修饰基因，所述工程突变是用源自129/Sv小鼠的ES（胚胎干）细胞制备的，并且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10个129.MOLF CSS的构建。这些品系对于研究这些品系之间的差异特征将是有价值的，这些品系来自10万年前分化的小鼠。这些菌株也可用于表征在这些小鼠中调节表型的修饰基因。这些CSS面板将通过促进QTL的检测和发现来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.