CORE--MOUSE GENETIC

描述(由申请人提供)： 系统性红斑狼疮(SLE)是一种系统性自身免疫性疾病，由 人类和小鼠模型中的多个基因。小鼠作为研究致病因素的模式生物的有用性已被广泛接受。到目前为止，已经有多达12个不同的基因座与小鼠狼疮有关，但1、4、7和17号染色体上有很强的遗传联系。新的可用的遗传工具正在改变小鼠模型中自身免疫性疾病的研究，并有可能支持对复杂的生理途径和遗传特征的合理探索。同源基因小鼠在这方面特别有用，因为它们可以在基因控制的实验中研究单基因或多个紧密连锁基因的影响，从而使定向和理性的方法能够研究多基因特征。此外，同源基因小鼠及其衍生的重组同源基因小鼠为基因定位和定位基因克隆策略提供了基础。最终，从对小鼠模型的研究中获得的信息和资源可能被用来识别和表征导致自身免疫性疾病的人类基因。为了让SCOR的成员能够使用这些遗传工具，我们建立了小鼠遗传学核心(MGC)。小鼠遗传学核心的主要作用是维护现有的小鼠模型，并根据服务于SCOR所有四个项目的SCOR首席研究人员的需要，开发和维护新的小鼠模型，用于研究具有良好特征和适当的遗传背景的自身免疫性疾病。新的同源基因、重组同源基因和基因靶向小鼠将使用一种“速度同源”策略，利用其他人和我们之前已经拥有的全基因组微卫星筛选集来生成 特色化的。特别是，MGC将作为一个育种单位和遗传分析设施，在小鼠中有效和可控地繁殖和选择特定的遗传性状或突变基因。基因特征将包括基因分型、微卫星连锁、DNA测序和基因表达分析。此外，MGC将作为一个教育资源，为SCOR调查人员及其实验室人员提供关于老鼠饲养和处理以及遗传特征方面的所有方面的信息和培训。因此，MGC将通过提供一个可操作的和集中的小鼠核心设施来满足SCOR研究人员的需求，以维护和开发继续进行SLE研究所需的小鼠模型，并将鼓励将生化和生理研究从细胞培养系统扩展到整个动物模型，促进基础研究与临床前研究的联系。

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is a systemic autoimmune disease process contributed by multiple genes in humans and mouse models. The usefulness of the mouse as a model organism for studies of factors that contribute to pathogenesis has been well accepted. To date, as many as 12 distinct loci have been implicated in mouse lupus, but strong genetic linkages have been assigned to chromosomes 1, 4, 7 and 17. Newly available genetic tools are transforming studies of autoimmune disease in mouse models and have the potential to support rational exploration of complex physiological pathways and genetic traits. Congenic mice are especially useful in this regard since they are amenable to the study of the effects of single genes or multiple tightly linked genes in genetically controlled experiments, thus enabling directed and rational approaches toward the study of multigenic traits. Moreover, congenic mice and recombinant congenic mice derived from them, provide the foundation for genetic mapping and positional gene cloning strategies. Ultimately, information and resources gained from investigation of mouse models may be exploited to identify and characterize human genes that contribute to autoimmune disease. In order to make these genetic tools available to the members of the SCOR, we have established the Mouse Genetics Core (MGC). The primary role of the Mouse Genetics Core is to maintain extant mouse models and to develop and maintain novel mouse models for studies of autoimmune disease in well characterized and appropriate genetic backgrounds as needed by SCOR Principal Investigators serving all four SCOR projects. Novel congenic, recombinant congenic and gene targeted mice will be generated using a "speed congenic" strategy utilizing genome-wide microsatellite screening sets that others and we have previously characterized. In particular, the MGC will serve as a breeding unit and genetic analysis facility for efficient and controlled propagation and selection of specified genetic traits or mutant genes in mice. Genetic characterization will include genotyping, microsatellite linkage, DNA sequencing, and gene expression analyses. In addition, the MGC will serve as an educational resource, providing information and training for all aspects of mouse breeding and handling and genetic characterization for SCOR Investigators and their laboratory personnel. Hence, the MGC will service the needs of the SCOR Investigators by providing an operational and centralized mouse core facility to maintain and develop the necessary mouse models for continued SLE investigation and will encourage expansion of biochemical and physiological studies from cell culture systems into whole animal models, facilitating linkage of basic research with preclinical studies.