The animal core provides a central mechanism by which consistent, high quality and cost effective access to important animal models is provided. Specific Objectives: 1a) Production, husbandry and genotyping of CFTR knockout mice. 1b) Production, husbandry and genotyping of mice with targeted mutations related to immune function or inflammation. 1c) Generation of new transgenic mice. 2) Assist investigators in the selection of mutant mice and train investigators in their appropriate use as models for gene therapy, or lung infection/inflammation relevant to CF and gene therapy of CF. 3) Purchase and provide small animals for pilot gene therapy experiments. 4) Provide baboons (or other relevant primates) for selected projects, to facilitate the acquisition of pre-clinical data in preparation for human trials. Objectives 1 and 2 are central to the functions of this core, since these objectives provide important mouse models for studies related to gene transfer to the lung and chronic inflammation and injury in the lung, as seen in CF. Objective 4 is an important intermediate step before moving potentially toxic or high risk approaches into human trials, which type of studies justify the use and expense of primates. Objective 3 provides limited numbers of normal mice or rabbits to the pilot projects. These objectives address the major demands for animal core services during the current period, focus on the high priority given to CF related work and develop new mouse mutants to address a major problem encountered in gene transfer studies, the immune and inflammatory response to vector and/or transgene.
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