TRANSGENIC AND TARGETED MUTANT PRESERVATION

这一竞争性的续约寻求继续为杰克逊提供资金 实验室（TJL）的诱导突变资源（IMR）继续提供 这种转基因和靶向突变小鼠的关键资源， 科学界。通过基因选择性改变小鼠基因组 转移（转基因小鼠），同源重组和时间和 诱导突变小鼠的组织特异性生产和应用 这些手段迅速扩大，增加了对资源的需求， 维持、保存和分发这些突变小鼠的健康状况， 地位和最低限度的限制。研究人员经常收到 要求他们创造的老鼠，并希望相信的负担， 把老鼠分发给其他科学家会影响他们的研究 方案和赠款。TJL成立于1929年，是一家非营利性研究机构。 研究机构，一直保持和分发突变品系的小鼠， 将近50年了1992年，TJL成立了IMR，其目的是 导入、冷冻保存和分配生物医学上重要诱导突变体 小鼠对IMR的需求是迫切的，其快速增长就是证据。 自成立以来，IMR已经接受了495个突变体股票，正在分发 其中299个，另外58个正在进口过程中。在 1997年，分发了近6万只老鼠。我们请求支持 再衍生、冷冻保存和菌株开发，以及菌株 发展以提高IMR小鼠品系的科学价值 都是为了分发给其他科学家， 尽可能的回收。为了改善IMR资源计划，我们建议 研究：（1）开发确保无病原体的方法 小鼠精子冷冻保存，（2）表型表征新的 诱导突变和转移到新的同类基因的突变 背景，和（3）开发更具有成本效益的基因分型方法。 对IMR小鼠的需求继续增加，与此同时， 随着几笔不可续延的启动赠款终止，的比率 拒绝接受的菌株正在增加（见导言）。的大小 需要超出了NCRR单独资助的范围。 已经通过机构内协议为这一努力做出了贡献。期间 在当前拨款的前4年，超过70%的小鼠由 IMR由16个NIH的NIH内部和外部受赠者接收 院所为了满足日益增长的需求，我们请求批准 扩大这一国家转基因和靶向小鼠资源， 授权NCRR从NIH研究所寻求额外的资金。以帮助 在审查中，我们对整个预算组成部分进行了细分。的 导言部分介绍了目前的供资机制和我们的建议， 在不给NCRR带来过多负担的情况下扩大IMR。

This competing renewal seeks continued funding for The Jackson Laboratory's (TJL) Induced Mutant Resource (IMR) to continue to provide this critical resource of transgenic and targeted mutation mice to the scientific community. Selectively altering the mouse genome by gene transfer (transgenic mice), homologous recombination and temporal- and tissue-specific production and use of induced mutant mice generated by these means has rapidly expanded, increasing the need for a resource to maintain, preserve, and distribute these mutant mice at a high health status and with minimal restrictions. Researchers frequently receive requests for mice they have created and want to believed of the burden that distributing mice to other scientists places on their research programs and grants. TJL, founded in 1929 as a non-profit research institution, has maintained and distributed mutant strains of mice for nearly 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 compelling and evidence by its rapid growth. Since it began, the IMR has accepted 495 mutant stocks, is distributing 299 of these, with another 58 currently in the importation process. In 1997, nearly 60,000 mice were distributed. We request support for rederivation, cryopreservation, and strain development, and strain development to improve the scientific value of strains in the IMR; 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 methods to assure pathogen-free cyropreservation of mouse sperm, (2) phenotypically characterize new induced mutations and mutations transferred to new congenic genetic backgrounds, and (3) develop more cost-effective genotyping methods. Demand for IMR mice continues to increase, coincident with a decline in funding as several non-renewable start-up grants terminate. The ratio of rejected to accepted strains is increasing (see Introduction). The size of the need is beyond the scope of the NCRR alone to fund. NIAID and NIAMS already contribute to this effort by Intra-Agency Agreements. During the first 4 years of the current grant, over 70% of the mice supplied by the IMR were received by NIH intramural and extramural grantees of 16 NIH Institutes. To address the growing need we request approval of an expansion of this national resource for transgenic and targeted mice to authorize the NCRR to seek additional funding from NIH institutes. To aid in review we have subdivided the overall budget components. The Introduction explains the current funding mechanisms and our proposal to expand the IMR without an excessive burden to the NCRR.