REFERRAL CENTER--ANIMAL MODELS OF HUMAN GENETIC DISEASE

点击翻译按钮获取中文摘要

The increasing possibilities for treating genetic disorders in human patients by approaches ranging from gene product replacement to gene transfer have created an increasing need for animal models in which to investigate pathogenetic mechanisms and approaches to therapy. The large reservoir of naturally-occurring counterparts of human genetic disease in animals has not been adequately utilized, largely because of the lack of accessible centers providing the special studies needed to identify genetic disorders in animals and establish their homology with human genetic diseases. In previous grant periods, we have demonstrated the value of such a center. The objective of this project is to continue to provide a national referral center for the identification, characterization, and dissemination of useful new animal models of human genetic disease. Emphasis in this proposal will be on monogenic human inborn errors of metabolism potentially correctable by gene therapy. The animal models sought among various species including murine, feline, and canine, will be true homologs of these human diseases (involve homologous gene loci and have disease characteristics comparable to the human disease). The center will provide consultation and laboratory studies of promising new models, including detection and identification of abnormal metabolites, cytogenetics, and special pathologic studies of biopsies and postmortem specimens. Family and breeding studies will be used to define modes of inheritance. Established new models will be made available to the general biomedical community in the form of cell cultures, DNA, frozen semen, and breeding stock. In selected monogenic metabolic disorders where the gene has not been cloned in the model species, we will clone the normal and mutant cDNA, characterize the mutation, and make the normal cDNA available for gene transfer studies.