Feline GM1 gangliosidosis, an inherited lysosomal disease of cats, is characterized by a profound deficiency of acid optimum Beta-galactosidase activity, neuronal accumulation of GM1 ganglioside, and visceral accumulation of glycoproteins. This fatal CNA disease of cats appears to be virtually an exact replica of juvenile GM1 gangliosidosis of children and, therefore, has exceptional value as an experimental animal model of the gangliosidoses and other lysosomal enzyme deficiency disorders of man. This project provides for preservation and expansion of a stock of mutant cats with GM1 gangliosidosis and use of this model in basic and applied research including: (a) characterization of the feline disease in clinical, morphological, genetic and biochemical terms, (b) establishment and utilization of a fibroblast culture system for in vitro studies, and (c) evaluation of a variety of promising in vivo therapeutic measures including organ transplantation. Recent advances made in the development of methods for purifying feline GM1 ganglioside Beta-galactosidase provides a unique opportunity for further exploiting this model by investigating the comparative physico-chemical properties of normal and mutant Beta-galactosidases. These studies will generate essential new knowledge about the molecular basis for lysosomal diseases. Results of these biochemical studies will be rapidly translated into data on functional significance by evaluating in vivo, the potential therapeutic effect of various biochemical manipulations of normal and mutant Beta-galactosidases.