TRANSGENIC & TARGETED MUTANT MICE PRESERVATION: BREEDING COLONIES: CRYOPRESERVE

描述(由申请人提供)： 这一竞争续签为杰克逊实验室(TJL)诱导的突变资源(IMR)继续寻求资金，以继续向科学界提供这一关键的转基因小鼠资源。通过基因转移(转基因小鼠)、同源重组、时间和组织特异性基因突变(基因打靶)和化学诱变来选择性地改变小鼠基因组，为生物医学研究提供了新的强大工具。这类小鼠的生产和使用迅速扩大，增加了对资源中心的需求，以保持、保存和分发它们处于高健康状态，并尽可能不受法律限制。研究人员经常收到如此多的关于他们的老鼠的请求，以至于他们必须减轻分发老鼠给他们的研究计划和拨款带来的负担。50多年来，TJL一直在维护和分发突变小鼠品系。1992年，TJL建立了IMR，其目的是进口、冷冻保存和分发具有生物医学意义的诱导突变小鼠。IMR的快速增长证明了对IMR的需求。自开始以来，IMR已经接受了950只突变种群，其中300只仍在从繁育群体中分发。剩下的菌株已作为冷冻胚胎或精子存档。另有120人目前正在进口过程中。在当前资助期的前4.5年，IMR分发了45万只小鼠；2002年，小鼠被分发给750名研究人员，并支持由几乎每个NIH分类研究所资助的研究。我们请求支持重新衍生、冷冻保存和菌株开发，以提高IMR菌株的科学价值；小鼠被维护以在尽可能多的成本回收的基础上分发给其他科学家。为了改进IMR资源计划，我们建议开展以下研究：(1)开发更可靠的精子冷冻和回收方法；(2)利用IMR中已有的适当报告菌株来鉴定表达Cre的菌株的组织和器官特异性表达；(3)对所选突变体进行进一步的表型鉴定，以提高其价值。IMR对菌株的接受与NCRR资助的突变小鼠区域资源中心(MMRRC)、美国国家癌症研究所人类癌症小鼠模型联盟(MMHCC)和欧洲突变小鼠档案馆(EMMA)协调，以避免资源重复。

DESCRIPTION (provided by applicant): This competing renewal seeks continued funding for The Jackson Laboratory's (TJL) Induced Mutant Resource (IMR) to continue to provide this critical resource of genetically engineered mice to the scientific community. Selectively altering the mouse genome by gene transfer (transgenic mice), homologous recombination and temporal- and tissue-specific gene mutation (gene targeting), and chemical mutagenesis is providing new and powerful tools for biomedical research. The production and use of such mice has rapidly expanded, increasing the need for resource centers to maintain, preserve, and distribute them at a high health status and as free from legal restrictions as possible. Researchers frequently receive so many requests for their mice that they must be relieved of the burden that distributing mice places on their research programs and grants. TJL has maintained and distributed mutant strains of mice for over 50 years. In 1992, TJL established the IMR whose purpose is to import, cryopreserve, and distribute biomedically important induced mutant mice. The need for the IMR is evidenced by its rapid growth. Since it began, the IMR has accepted >950 mutant stocks, of which >300 are still being distributed from the breeding colony. The remaining strains have been archived as frozen embryos or sperm. Another 120 are currently in the importation process. In the first 4.5 years of the current grant period, the IMR distributed >450,000 mice; in 2002 mice were distributed to 750 investigators and supported research funded by nearly every NIH categorical institute. We request support for rederivation, cryopreservation, and strain development to improve the scientific value of IMR strains; mice are maintained for distribution to other scientists on as much of a cost recovery basis as possible. To improve the IMR resource program we propose to do research to (1) develop more reliable methods of sperm cryopreservation and recovery, (2) characterize the tissue- and organ-specific expression of Cre-expressing strains by using appropriate reporter strains already present in the IMR, and (3) carry out further phenotype characterization of selected mutants to enhance their value. IMR acceptance of strains is coordinated with the NCRR-funded Mutant Mouse Regional Resource Centers (MMRRC), the National Cancer Institute Mouse Models of Human Cancer Consortium (MMHCC), and the European Mutant Mouse Archive (EMMA) to avoid duplication of resources.