Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Abstract

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 include cytoplasmic vacuolation in the nervous system and viscera, and myelin deficits that demonstrate regional variation. This study was designed to determine the correlation between beta-mannosidase activity in normal animals and the severity of lesions in affected goats, and to 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 with the accumulation of uncatabolized substrate and with the extent of vacuolation, this correlation does not extend to assessment of specific regions of the central nervous system (CNS). In affected goats, the activities of alpha-mannosidase, alpha-fucosidase, and beta-hexosaminidase are elevated to a greater extent in all CNS regions than in organs. The 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 activity.

BIOCHEMICAL AND MORPHOLOGICAL EXPRESSION OF EARLY PRENATAL CAPRINE Β-Mannosidosis

“…In V385, kidney -hexosaminidase activity was elevated 1·7 times above the mean. The elevations in V385 are consistent with the extent of elevations of these lysosomal enzyme activities, compared with control values, in kidney of newborn -mannosidasedeficient goats (Lovell et al, 1994).…”

“…Samples (0·1 g) of kidney, brain, and liver were prepared and specific activities of -mannosidase, -mannosidase, and -hexosaminidase were determined as previously described (Lovell et al, 1994). Thin-layer chromatography (TLC) was used to determine the presence of accumulated di-and trisaccharides in kidney and brain samples (0·1 g) as previously described (Matsuura et al, 1981).…”

Distribution and Severity of Neuropathology in β-Mannosidase-Deficient Mice is Strain Dependent

“…Some areas that were vacuolated did not show increased expression, and some regions with higher expression (e.g., Purkinje cells in cerebellum) did not show vacuolation. In general, b-mannosidase has very low expression throughout the CNS in mice (Lein et al 2007) and in goats (Boyer et al 1990;Lovell et al 1994) compared to that of other glycoprotein catabolic enzymes. There is no apparent consistent correlation among gene expression, enzyme activity, and severity of vacuolation.…”

Novel synthesis of mannosamine conjugated magnetic nanoparticles for purification and stabilization of human lysosomal β-mannosidase

“…Among them, β-mannosidase is involved to remove the terminally linked D-mannose residue from nonreducing end. β-mannosidase enzyme has been purified and characterized from many sources [1,[6][7][8]11,15] through cumbersome procedures using whole cell extract. The purity and activity of the enzyme is necessary for structural and functional studies.…”

“…In β-mannosidosis, the accumulation of undegraded di and trisaccharide, and oligosaccharide of mannosyl-N-linked glucosamine are found in fibroblast, leukocytes, brain, kidney, and liver [4,[14][15]. β-mannosidosis cases have been identified and characterized in goat [16], bovine [17,18], as well as in humans [19][20][21].…”