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.