Many Individual Projects of the proposed Silvio O. Conte Center for Neuroscience Research (CCNR) at MIT require genetically engineered mice. Furthermore, many of these mice are proposed to be generated and/or analyzed in collaborative arrangements involving two, three or even four laboratories. Another characteristic feature of these mice is that many of them are conditionally engineered and, therefore, require crossing of two or three component strains that are modular (e.g., Cre, floxed, tTA and Otet mice). Many of these component mice are crossed in different combinations for different specific aims across multiple collaborative projects. Therefore, we propose to set up central breeding colonies of these component mice at MIT in collaboration with its Department of Comparative Medicine which supervises and services MIT's entire animal facility. The central colonies are meant to be for the maintenance of the various strains and occasional supplying of these strains to individual laboratories. The cost for the intercrossing of mice to be used in specific experiments described in the Individual Projects will be charged to the individual faculty's budget. The mutant and transgenic mice to be produced, maintained, and used in Heinemann's lab at the Salk Institute will be charged to his individual budget. The cost to generate the strains described in Core #1 and individual projects will be charged to the corresponding budgets. Only after the component mice are established will they be transferred to Core #2 for maintenance. The mouse holding space will be provided by MIT. The standard maintenance services, cage changes, bedding, food, water, and health monitoring will be provided by the staff of the Department of Comparative Medicine for which the Core will pay per diem charges. In Year 1 about 15 to 20 strains will be maintained and we expect that about 10 strains will be added in subsequent years as they are newly made. It is expected that some colonies such as fNR1, CA1-Cre, and CA3-Cre, will be relatively large (50 cages) because of the heavy demands from multiple projects while others such as global NR1 KO, global GluR6 KO, and CA3-NR1 KO mice to be used occasionally as a control will be kept small (10 cages). The service provided by this Core consists of (1) maintenance of the colonies, (2) genetic typing of individual mice, and (3) shipment of mice to the Salk Institute and other outside collaborators. Core #2 will permit supplies of identically maintained mouse strains to the collaborating labs within the Center and sometimes beyond the Center.

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