TRANSGENIC AND TARGETED MUTANT PRESERVATION

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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.