Animal models of human disease are a critical component in the development of effective gene therapies. Genetically defined animal models which reproduce the clinical manifestations of a disease help to elucidate the pathophysiologically relevant cellular targets for gene therapy and aid in development and testing of gene vector technologies for therapeutic efficacy. The Animal Models Core will provide support to investigators using animal models for the development of gene therapies for several genetic diseases with an emphasis on cystic fibrosis. In this regard, the Core will provide centralized production, care, breeding, genotyping and quality control of transgenic and knockout animals for use by investigators in the Center. The core will also provide a mechanism for the receipt or distribution of new experimental transgenic and knockout models with the Jackson Laboratory Induced Mutant Resource, a national resource for transgenic and knockout mice, to Center investigators. BL2 animal containment facilities for experiments with recombinant viruses will also be consolidated within the Core for use by investigators of the Center. For CF-based research, the core will provide several animal models for cystic fibrosis, including colonies of CF mice which harbor either null or clinically relevant point mutations, and human bronchial xenografts. These models will play a large programmatic role for studies on CF airway pathogenesis and gene therapy. In addition to the obvious emphasis this Center will have in gene vector development, it is also recognized that a concrete understanding of CF airway pathophysiology is also critical to the overall goals of this Center. Such information on the basic pathobiology of CF airway disease will lead to the identification of the relevant cellular targets and CFTR functions in the lung necessary for successful gene therapy approaches. Although this Core plans to direct the majority of its efforts toward gene therapy of cystic fibrosis, it will also play a broader role in the development of gene therapies for several other genetic diseases of programmatic emphasis to this Center. The main responsibilities of the Core will be: . Generation of transgenic mice . Generation of gene-targeted mice . Genotyping transgenic and knockout animals . Rederival of genetic stocks . Maintenance, cryopreservation, and provision of genetic stocks . Quality control of genetic lines . Generation of human bronchial xenograft models.
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