The objective of this project is to discover and characterize mouse models of human inherited diseases. Mice from the Jackson Laboratory with relevant clinical signs of disease will be screened for lysosomal storage diseases, disorders of amino acid metabolism and organic acidemias. The mice to be screened include over 50 established mutants with unknown biochemical defects and approximately 300 phenotypic deviant mice that arise in the inbred mouse production colonies. The mice are screened by established procedures which include histopathology, quantitative serum amino acid analysis and analysis of urine organic acids by gas chromatography-mass spectrometry. All mice with metabolic mutations detected by the screening procedures will be characterized further by detailed study of clinical characteristics, genetics, pathology and biochemical identification of the abnormal enzyme and metabolites. The long-term goal of this project is to develop well characterized mouse models for research. The pathobiology of most inherited diseases is understood poorly and these models could provide new research approaches. Likewise, critical questions could be answered with mouse models concerning highly controversial therapy regimens such as bone marrow transplantation for lysosomal storage diseases or gene therapy for many metabolic disorders. Most of these human disorders have no animal model and this project is designed to fill that deficit.
