CORE--MOUSE GENETIC

核心--小鼠遗传

• 批准号: 6663947
• 负责人: Michael G Brown
• 金额: $ 21.7万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6663947
• 关键词: animal breeding; animal colony; biomedical facility; disease /disorder model; genetic models; genetically modified animals; genotype; laboratory mouse; model design /development; polymerase chain reaction; systemic lupus erythematosus; transfection

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.

描述（由申请人提供）： 系统性红斑狼疮（SLE）是一种全身性自身免疫性疾病， 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。迄今为止，多达12个不同的基因座与小鼠狼疮有关，但强烈的遗传连锁已被分配给染色体1，4，7和17。新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生理途径和遗传特征的合理探索。同源小鼠在这方面特别有用，因为它们适合于在遗传控制实验中研究单个基因或多个紧密连锁基因的作用，从而使针对多基因性状的研究的定向和合理的方法成为可能。此外，同类小鼠和由它们衍生的重组同类小鼠为遗传图谱和定位基因克隆策略提供了基础。最终，从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。为了使这些遗传工具提供给SCOR的成员，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存的小鼠模型，并根据服务于所有四个SCOR项目的SCOR主要研究者的需要，开发和维护用于自身免疫性疾病研究的新型小鼠模型。新的同源，重组同源和基因靶向小鼠将产生使用“速度同源”的战略，利用全基因组微卫星筛选集，其他人和我们以前 表征了特别是，MGC将作为育种单位和遗传分析设施，用于有效和受控地繁殖和选择小鼠的特定遗传性状或突变基因。遗传表征将包括基因分型、微卫星连锁、DNA测序和基因表达分析。此外，MGC将作为教育资源，为SCOR研究人员及其实验室人员提供小鼠育种和处理以及遗传表征的各个方面的信息和培训。因此，MGC将通过提供可操作的和集中的小鼠核心设施来满足SCOR研究者的需求，以维持和开发持续SLE研究所需的小鼠模型，并将鼓励将生化和生理学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。