CYSTEINE DIOXYGENASE TRANSGENIC MOUSE MODEL

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Abnormal or deficient cysteine dioxygenase (CDO) activity has been claimed to be seen in individuals with a variety of chronic diseases, both non-neurological and neurological, that are associated with aging. Low CDO activity may result in pathologies, either because of an insufficient supply of sulfate or taurine, products of cysteine catabolism, or because of accumulation of cysteine or toxic metabolites. Evidence for polymorphisms in the CDO gene has been reported in the human population. Data from patients with rheumatoid arthritis, Parkinson's disease, Alzheimer's disease, motor neuron disease, and other diseases, suggest that low CDO activity may be associated with the occurrence, severity, or speed of progression of these diseases. Our specific aims are: 1. To clone and characterize the murine COD gene. 2. To develop a CDO transgenic/knock-out mouse model of low or absent CDO activity for study of the role of variations in CDO activity on nutritional requirements (especially for cysteine, taurine and sulfate) and in predisposition of individuals to certain degenerative diseases. Our long term goals are: 1. To determine the relationship of tissue CDO activity to tissue and plasma cysteine, glutathione, sulfate and taurine levels and to urinary taurine and sulfate levels with the goal of identifying noninvasive parameters that would allow the study of variations CDO activity in human populations. 2. To study the relationship of CDO activity to chronic degenerative disease.