A Carolina Center to Characterize and Maintain Mutant Mice

描述（由申请人提供）：由于人类和小鼠基因组的完成以及小鼠技术的进步，小鼠突变体和人类疾病模型的数量大幅增加。维持和分发无病原体的小鼠品系是一项劳动密集型的工作，对于个体研究者来说，长期维持是一项昂贵的工作。NIH/NCRR认识到有必要为转基因小鼠建立一个共同的储存库和分配中心，并于1999年资助了突变小鼠区域资源中心（MMRRC）。北卡罗来纳大学教堂山分校是为整个生物医学界开发这一资源的三个MMRRC中心之一。自1999年启动并于2005年重新获得资助以来，在创建组织基础设施和建立标准操作程序（sop）方面投入了大量精力，用于突变小鼠品系的输入、再衍生、表型分型、冷冻保存和分发。2001年，MMRRC-UNC接收了第一株菌株，截至2009年，三个中心已存档1639株菌株，可供分发。与此同时，MMRRC-UNC还利用UNC的专业知识，为社区带来了新的技术和资源，如突变es细胞系、突变菌株和改进的体外受精方法。为了满足未来对MMRRC服务的需求并改进现有技术，本提案旨在：(1)简化转基因小鼠品系的导入、存档和分发程序；(2)研究小鼠精子低温保存的氧化损伤机制；(3)将协作杂交小鼠存档并整合为MMRRC收藏。

DESCRIPTION (provided by applicant): Due to the completion of the human and mouse genomes as well as advances in mouse technologies, there has been an enormous increase in the number of mouse mutants and models for human disease. Maintaining and distributing pathogen-free mouse strains is both labor-intensive and costly for individual investigators to sustain long term. The NIH/NCRR recognized the need for a common repository and distribution center for genetically modified mice and in 1999 they responded by funding the Mutant Mouse Regional Resource Centers (MMRRC). UNC-Chapel Hill is one of three MMRRC centers that has been developing this resource for the benefit of the entire biomedical community. Since initial funding began in 1999 and was renewed in 2005, a significant amount of effort has been invested in creating the organizational infrastructure and establishing standard operating procedures (SOPs) for importation, rederivation, phenotyping, cryopreservation and distribution of mutant mouse strains. In 2001, the MMRRC-UNC accepted the first strain and as of 2009,1639 strains have been archived by the three centers and are available for distribution. In parallel with these efforts, the MMRRC-UNC has also taken advantage of the expertise available at UNC to bring new technologies and resources to the community such as mutant ES-cell lines, mutant gnotobiotic strains, and improved in vitro fertilization methods. To meet future demands for MMRRC services and improve upon existing technologies, this proposal aims to: (1) Streamline procedures to import, archive and distribute genetically modified mouse strains, (2) Investigate the mechanisms of oxidative damage in cryopreserved mouse sperm, and (3) archive and integrate Collaborative Cross mice as an MMRRC collection.