TRANSGENIC AND TARGETED MUTANT PRESERVATION

这一相互竞争的续约为杰克逊寻求持续的资金 实验室(TJL)诱导突变资源(IMR)继续提供 这一转基因和靶向突变小鼠的关键资源 科学界。用基因选择性地改变小鼠的基因组 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使用 这些手段迅速扩展，增加了对资源的需求 保持、保存和分发这些突变的小鼠保持高度健康 身份和最低限度的限制。研究人员经常收到 对自己创造的老鼠的要求，并希望相信自己的负担 把老鼠分发给其他科学家是他们研究的重点 计划和赠款。TJL成立于1929年，是一家非营利性研究机构 机构，维护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、冷冻保存和分发具有重要生物医学意义的诱导突变 老鼠。IMR的快速增长证明了对IMR的需求是令人信服的。 自开始以来，IMR已经接受了495个突变种群，正在分发 其中299人，另有58人目前正在进口过程中。在……里面 1997年，分发了近6万只老鼠。我们请求支持 再衍生、超低温保存、菌株发展和菌株 提高IMR；小鼠品系科学价值的研究进展 以同样的成本分发给其他科学家 尽可能在恢复的基础上。为了改进IMR资源计划，我们提出了 研究：(1)开发确保无病原体的方法 小鼠精子的冷冻保存，(2)新的表型特征 诱发突变和转移到新的同源基因的突变 背景；(3)开发更具成本效益的基因分型方法。 对IMR鼠标的需求继续增加，同时 随着几笔不可续期的启动赠款终止，这笔资金将被取消。的比例 被接受的菌株被拒绝的情况正在增加(见导言)。的大小 这一需求超出了NCRR单独提供资金的范围。NIAID和NIAMS 已经通过机构内协议为这一努力做出了贡献。在.期间 在目前赠款的前4年，超过70%的老鼠是由 接受IMR的是16名NIH的壁内和壁外受赠者 研究所。为了满足日益增长的需求，我们请求批准 将这一国家转基因和靶向小鼠资源扩大到 授权NCRR向NIH研究所寻求额外资金。去帮助 在审查过程中，我们细分了总体预算组成部分。这个 引言解释了目前的资助机制和我们的建议 在不给NCRR带来过重负担的情况下扩大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.