TRANSGENIC MOUSE MODELS OF HUMAN METABOLIC DISEASES

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Animal models are needed desperately if significant progress is to be made in understanding pathophysiological mechanisms, molecular genetics and therapy of human metabolic diseases. Recent developments in molecular genetics provide the opportunity to create specific analogs of human metabolic diseases in laboratory rodents. Using technology for introduction, stable integration and expression of DNA mediated anti-sense RNA, we propose to demonstrate inhibition of lysosomal Beta-glucuronidase in transgenic mice with expression of lysosomal storage disease resembling mucopolysaccharidosis VII. Successful demonstration of the feasibility of this approach will lead to development of transgenic mouse models of other metabolic diseases for which mutant genes have been cloned and characterized, such as Gm2 gangliosidosis (Tay Sachs disease). This innovative new approach could dramatically advance research on human matabolic diseases by providing critically needed models to define disease mechanisms and develop treatment modalities.