The function of the Animal Model Core is to provide complete services in the production and characterization of all forms of transgenic and mutant mice and stem cell lines and to centralize these functions together with other embryo micromanipulation and transfer activities for economies of space and scale. To accomplish this goal, the Core will perform the following: generation, culture, and cytogenetic monitoring of embryonic stem (ES) cell lines; transfection of cloned DNA into ES cells for the production of transgenic and homologously recombined cells; selection of transfected ES cells and injection into preimplantation embryos (8 cell- and blastocyst) to produce ES cell chimeras; injection of cloned DNA into fertilized oocytes for the production of transgenic animals; transfer of transgenic embryos or of transgenic or homologously-recombined ES cell chimeras into pseudopregnant foster females; initial characterization of transgenic and mutant progeny;establishment and maintenance of the initial breeding stock of transgenic and mutant mice; maintenance of breeding stocks of mutant mice imported from elsewhere. All mice used and generated will be housed in the UCSF Transgenic Facility. This facility is a new, shared, multi-user barrier facility constructed inside the UCSF Animal Care Facility for the purpose of studies on transgenic mice. A micromanipulation and ES cell culture station will be established to carry out all technical work required to generate transgenic and mutant mice. Routine cytogenetic monitoring and tests for chimera formation and germ line transmission will be undertaken for all stem cell lines used, and the media and LIF (leukemia inhibitory factor) required for stem cell culture will be routinely tested to determine optimal conditions for stem cell growth. Similarly, monitoring of the media used for preimplantation embryo culture will also be carried out. The personnel of the core will undertake an active program to educate all investigators related to this grant in the approaches required for the construction of transgenic and homologous- recombination "knockout" mice. When appropriate, the core will work with investigators to develop net approaches to the construction of such animals.