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This project aims to establish suitable animal models (e.g., mouse strains that develop osteoarthrosis, achalasia, etc.) for the study of human chronic diseases; to develop highly sensitive in vivo systems to evaluate carcinogenicity, mutagenicity, and teratogenicity of environmental and therapeutic agents; and to produce severe combined immunodeficient (SCID) mice for maintaining human organs and tissues. These model systems will be used to (a) perform pathological and genetic analyses; (b) conduct validation and demonstrative research for drug discovery and safety studies; (c) develop mouse strains that are reliable and easy to handle; and (d) promote education and training of researchers in these biomedical fields.