BIOCHEMICAL AND HISTOCHEMICAL ANALYSIS OF LYSOSOMAL-ENZYME ACTIVITIESIN CAPRINE BETA-MANNOSIDOSIS

Goats affected with beta-mannosidosis, an autosomal recessive disease of glycoprotein catabolism, have deficient tissue and plasma levels of the lysosomal enzyme beta-mannosidase. Pathological characteristics i nclude cytoplasmic vacuolation in the nervous system and viscera, and myelin deficits that demonstrate regional variation. This study was de signed to determine the correlation between beta-mannosidase activity in normal animals and the severity of lesions in affected goats, and t o assess the regional changes in lysosomal enzyme activity in specific regions and cell types in affected animals. Although enzyme activity in normal organs (kidney, thyroid, brain) is correlated in general wit h the accumulation of uncatabolized substrate and with the extent of v acuolation, this correlation does not extend to assessment of specific regions of the central nervous system (CNS). In affected goats, the a ctivities of ce-mannosidase, alpha-fucosidase, and beta-hexosaminidase are elevated to a greater extent in all CNS regions than in organs. T he results suggest cell-specific, organ-specific, and enzyme-specific regulation of changes in lysosomal enzyme activity in the presence of metabolic perturbations, such as deficiency of beta-mannosidase activi ty.