Canine GM2 gangliosidosis: morphological and biochemical analysis.

Beta-hexosaminidase activity and the effects of ganglioside storage on neuronal function were examined in a German shorthair pointer (GSHP) with progressive neurodegenerative signs. Morphologic evidence of neuronal storage and massive accumulation of GM2 ganglioside were present. Beta-hexosaminidase activity in plasma, liver, kidney, and brain, assayed with use of unsulfated fluorogenic substrates, was normal. There was no pathologic accumulation or aberrant localization of phosphorylated neurofilaments in neurons. Activity of cortical neurotransmitter synthesizing enzymes, choline acetyltransferase, and glutamate decarboxylase was unaffected. Ligand binding to carrier sites for choline high affinity uptake identified with [3H]hemicholinium-3 was increased, whereas post-synaptic binding to muscarinic cholinergic ([3H]QNB) and gamma-aminobutyric acid receptors ([3H]muscimol) was reduced.