Myelin-associated glycoprotein (MAG) in myelin deficiency of caprine β-mannosidosis

Abstract

Caprine β-mannosidosis is an inherited lysosomal storage disorder due to a deficiency of β-mannosidase which cleaves β-linked mannose residues from the ends of N-asparagine linked oligosaccharides of glycoproteins. Histological and chemical examination has revealed a deficiency of compact myelin in the brains and spinal cords of affected goats. Since myelin-associated glycoprotein (MAG) is glycosylated and its metabolism could be directly affected in this disease, we investigated the possibility of a differential treatment of MAG in caprine β-mannosidosis in comparison to non-glycosylated myelin proteins. MAG, myelin basic protein (MBP), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP), proteolipid protein (PLP) and glial fibrillary acidic protein (GFAP) were quantified by western blot analysis in whole homogenates of spinal cords and hemispheres from affected goats at 1,4 and days of age and from normal controls. The yields of isolated myelin from the spinal cords of affected goats varied from 37 to 63% of normal and were 7% or less of normal from the hemispheres. In mutant spinal cords, the deficits of MAG, CNP and PLP measured in whole homogenates corresponded reasonably well with the decreased myelin yields, but the levels of MBP were consistently much closer to control levels than those of the other myelin proteins. A greater deficiency of PLP than MBP was also apparent in the myelin fractions purified from the affected spinal cords. In homogenates of mutant hemispheres, MAG, MBP, PLP and CNP were undetectable or at trace levels in comparison to controls. There was no indication of preferential involvement of MAG in this disorder, since the MAG deficiency was comparable to that of other unglycosylated myelin proteins, and its apparent molecular weight was the same as that of controls on SDS gels suggesting normal glycosylation. GFAP was increased (115–150% of the control level) in most tissue samples from the affected goats indicative of astrocytosis.