Myelin Basic Protein Deficit in the PNS of <i>mld</i> Mutant Mice Recovers during Development

Abstract

Myelination was studied between 15 and 135 days postnatally in peripheral nerves of myelin deficient (mld) mice and in unaffected littermates. The nerve weights were not affected by the mutation and showed a 4-fold increase during the developmental period studied. The amounts of myelin present in peripheral nerves, as shown by biochemical and morphological techniques, were slightly reduced in mld in comparison to control mice. In controls, the concentration of myelin doubled during the investigation period. The increase of myelin basic protein (MBP) in total nerve homogenate paralleled the deposition of myelin, but the MBP concentration remained constant in normal myelin. In contrast, in mld myelin MBP concentrations were extremely low until 60 days of age and increased thereafter to reach almost normal values at 135 days. Similarly, the amounts of myelin isolated at 85 and 135 days were normal. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP; EC 3.1.4.37), the myelin-specific enzyme, showed normal specific activities in mld nerves. In mld and control myelin, CNP-specific activities decreased during development suggesting a preferential localization of CNP in Schwann cell plasma membranes. In contrast to the central nervous system, other myelin proteins were not altered in mld peripheral nervous system (PNS) and the very low MBP content had no severe repercussions on the composition and structure of the myelin sheath. Furthermore, Schwann cells appeared normal in mld PNS. Nevertheless, more subtle alterations could be detected. Slightly decreased amounts of myelin were observed in young mld mice and preliminary results indicate discrete alterations of the myelin periodicity. After 60 days postnatally, when the repressed MBP synthesis was removed, MBP was incorporated into the myelin sheath and the MBP deficit was nearly corrected.

Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice

“…Myelinating Schwann cells express MBP and MAG, which are required for peripheral nerve myelin formation and involved in both experimental and human demyelinating disease (Ginalski-Winkelmann et al, 1983, Farhadi et al, 2003). Neurofilaments are critical components of axons and reduction of neurofilaments in diabetic neuropathy have been reported (Yagihashi et al, 1990, Scott et al, 1999).…”

Intrinsic Myelin Proteins Are Normally Synthesized in vitro in the Myelin-Deficient <i>(mld)</i>Mutant Mouse

“…Developmental studies have shown that the concentration of MBP in total brain and peripheral nerve homogen ates increases after 60 days postnatally, sug gesting a gene regulation defect in mid mice with late and partial suspension of the repres sion [7,15,16]. The concentration of other myelin proteins, like proteolipid protein (PLP) and intermediate protein (I, also called DM-20) is also decreased, but to a les ser degree than that of MBP.…”

Three ATPase Activities Have an Abnormal Developmental Time Course in Trembler Sciatic Nerves

“…The concentration of the myelin marker myelin basic protein doubles in the PNS of control mice between 15 and 135 days of age [30]. The activity of the nonmitochondrial Mg2+-ATPase increased similarly during de velopment in normal nerves.…”