Myelin‐Associated Glycoprotein and Other Proteins in Trembler Mice

Abstract

The myelin-associated glycoprotein (MAG) and other myelin proteins were quantitated in homogenates of whole sciatic nerve from adult and 20-day-old Trembler mice. In the nerves of adult mice, the concentration of MAG was increased from 1.1 ng/.mu.g of total protein in the controls to 1.4 ng/.mu.g protein in the Tremblers. The concentrations of P0 glycoprotein and myelin basic proteins [MBP] were reduced to 27% and 20% of control levels, respectively. Immunoblots demonstrated that P2 was also greatly reduced in the Trembler nerves. The specific activity of 2'',3''-cyclic nucleotide 3''-phosphodiesterase (CNP) was 65% of the control level. Immunoblot analysis showed that MAG had a higher than normal apparent MW in the sciatic nerves of the Trembler mice, but its apparent MW was normal in the brains of these mutants. In 20-day-old Tremblers, the P0 and MBP were reduced slightly less to .apprx. 40% of the level in the nerves of age-matched controls. CNP and MAG levels were not significantly different from those in controls and MAG exhibited a shift toward higher apparent MW similar to that in the adults. The maintenance of high MAG levels despite the severe deficit of myelin, as reflected by the decrease of the major myelin proteins, is consistent with the immunocytochemical localization of MAG in periaxonal Schwann cell membranes, Schmidt-Lantermann incisures, lateral loops and the outer mesaxon and its absence from compact myelin. The abnormal form of MAG in the peripheral nervous system (PNS) of the Trembler mice may contribute to the pathology in this mutant.