The Transgenic Mouse Core (Core C) will service the transgenic mouse needs of the component projects of this PPG. The primary rationale for this transgenic mouse core is to ensure that individual projects have a consistent and reliable source of planned strains of transgenic mice in a cost-effective and efficient manner. The transgenic mouse colonies will be maintained at Taconic labs to ensure that the mice will be available to any academic lab without the expense and delay of the health/quarantine requirements for the transfer of mice between academic institutions. This is particularly important, as Core C will serve 4 academic institutions. Core C will achieve these functions via three specific aims:
Specific Aim 1 : Coordinate establishing transgenic strains at Taconic as required by the PPG. 1.1 Coordinate depositing at Taconic the five transgenic mouse strains currently available from Project leaders and collaborators. In addition, Project 1 (LaDu) currently maintians five transgenic strains at Taconic that are ready for use by the PPG. The specific strains and sources are listed in Figure 1 and Table 1. These 10 strains are described in Preliminary Data 1.2 Oversee the timely transfer of the new transgenic lines (ApoER2-Tg and LDLR-Tg) generated by Core B (Bu, Washington University Mouse Genetics Core facility) to Taconic. 1.3 Generate the crosses between PDGF-APP-Tg mice and ApoER2-Tg, ApoER2-KO, LDLR-Tg, LDLR-KO, mLRP-Tg, mLRP-KO, LDLR-Tg, LDLR-KO, resulting in six new transgenic strains. These 8 new transgenic strains referred to in sub-aim 1.2 and 1.3 are described in the Design Section. Dr. Weeber (Project 5) will perform behavioral and neuroplasticity characterization of these strains.
Specific Aim 2. Ensure availability of requested adult and timed pregnant animals for the program projects. Mouse breeding and colony maintenance of the 18 transgenic strains described above as well as wild type mice, will require a systematic approach resulting from regular communication between the Core C staff and the Taconic collaborators, including quarterly updates of projected animal use by the projects and on- going adaptations to the breeding strategies. This will ensure the timely supply of mice to the various projects. By overseeing all mouse activity going between Taconic and the projects, Core C will aide in maximizing experimental use of valuable transgenic mouse resources.
Specific Aim 3. Make PPG-generated transgenic strains available to the broader scientific community. The obvious """"""""innovation"""""""" or """"""""extrinsic merit"""""""" of this approach is that under the NIH guidelines, all the transgenic mouse strains developed as part of this program will be available to the general research community. The new mice developed by this PPG and its project leaders can be deposited at no cost in the Alzheimer's Disease Mouse Model Center (Jackson Laboratories).
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