It is now possible to isolate genes involved in genetic diseases and understand disease mechanisms in terms of the underlying molecular derangements, and there are encouraging new prospects for therapy for genetic diseases, including gene therapy. The full scope of understanding and treating genetic diseases in human patients cannot be realized without authentic (gene-homologous) animal models for studies not possible for ethical and practic_ reasons in human patients. Mouse gene knockout technology has provided a valuable source, but additional models are needed for studies requiring tong-lived animals of larger size to be able to monitor clinical signs and with phenotypes more closely resembling the human diseases. A large reservoir of such models is present in existing animal populations and can be studied with the cooperation of breeders, veterinarians, and others interested in genetic disease control. We have shown that this resource can be utilized by providing an accessible center to ascertain, verify, and preserve these models. The objective of this project is to continue to serve as a National Referral Center to identify, characterize, and make available for research, new animal models of human genetic disease. The models sought among laboratory, domesticated, and wild species including primates, will involve defects in homologous gene loci having essentially the same molecular and clinical phenotypes as in human patients. Models offering new opportunities to investigate disease pathogenesis and approaches to therapy will be emphasized. The Center will provide the clinical, pathologic, and molecular genetic studies required to establish homology with the human disorder. Verified models will be made available in the form of DNA, cells, frozen semen, breeding stock, and in selected models, normal and mutant cDNAs.