Feline GM₁, gangliosidosis: Biochemical and ultrastructukal comparisons with the disease in max

Biochemical and ultrastructural findings in a Siamese cat with GM₁ gangliosidosis have been presented and compared with the analogous disease in man, Type II GM₁ gangliosidosis. In both species there is marked accumulation of GM₁ ganglioside in cerebral cortex. The degree of gangliosidc accumulation and distribution of major gangliosides in brain of diseased cat and child arc remarkably similar. Beta-galaetosidase activity with a pH optimum of 3.8 was found to be markedly deficient in brain and kidney of the diseased cat. A second Beta-galaetosidase with a pH optimum of 5.0 was present at normal levels of activity in kidney of the diseased cat. Reduced activity of only one of two Beta-galactosidascs has also been observed in children with Type II GM₁ gangliosidosis. Certain features of the feline mutant Beta-galaetosidase activity including, heat inactivation, differences in apparent Michaelis' constant and differential response to the inhibitor galactono-(1 → 4)-lactone suggest that decreased measurable enzymatic activity may be the result of structural alteration in the enzyme. The ultrastructure of lamellar inclusion bodies present in cytoplasm of neurons from the diseased cat's brain were similar to those found in neurons of children with gangliosidc storage diseases. Feline GM₁ gangliosidosis appears to represent an animal model of exceptional value for the study of basic mechanisms of inherited defects of gangliosidc metabolism and may also greatly facilitate investigation of therapeutic intervention in these diseases.