TRANSGENIC & TARGETED MUTANT MICE PRESERVATION: BREEDING COLONIES: CRYOPRESERVE

描述（由申请人提供）： 这一竞争性的更新旨在为杰克逊实验室（TJL）的诱导突变资源（IMR）继续提供资金，以继续为科学界提供这种关键的基因工程小鼠资源。通过基因转移（转基因小鼠）、同源重组和时间和组织特异性基因突变（基因靶向）以及化学诱变来选择性改变小鼠基因组，为生物医学研究提供了新的强大工具。这种小鼠的生产和使用已经迅速扩大，增加了对资源中心的需求，以维持、保存和分发它们处于高健康状态并且尽可能不受法律的限制。研究人员经常收到如此多的老鼠需求，以至于他们必须减轻分发老鼠给他们的研究计划和赠款带来的负担。50多年来，TJL一直保持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重要性的诱导突变小鼠。IMR的快速增长证明了其必要性。自成立以来，IMR已经接受了超过950个突变体种群，其中超过300个仍在从育种群体分发。其余菌株已作为冷冻胚胎或精子存档。另外120个正在进口过程中。在当前资助期的前4.5年，IMR分发了超过450，000只小鼠; 2002年，小鼠被分发给750名研究人员，并支持几乎所有NIH分类研究所资助的研究。我们请求支持再衍生、冷冻保存和菌株开发，以提高IMR菌株的科学价值;小鼠被保留，以尽可能多的成本回收为基础分发给其他科学家。为了改善IMR资源计划，我们建议进行研究，以（1）开发更可靠的精子冷冻保存和恢复方法，（2）通过使用IMR中已经存在的适当报告菌株来表征Cre表达菌株的组织和器官特异性表达，以及（3）对选定的突变体进行进一步的表型表征以提高其价值。IMR接受菌株与NCRR资助的突变小鼠区域资源中心（MMRRC），国家癌症研究所人类癌症联盟小鼠模型（MMHCC）和欧洲突变小鼠档案（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 The remaining strains have been archived as frozen embryos or sperm.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.