Dysmyelination in mice and the proteolipid protein gene family.

Abstract

Myelin is a cellular specialization of vertebrate neuroglia which provides the physical basis for rapid impulse conduction: by electrically insulating axonal segments, myelin sheaths restrict action potentials to the nodes of Ranvier, resulting in myelinated axons that transmit signals up to 100 times faster than non-myelinated fibers of equal caliber. In the central nervous system (CNS), this function is provided by oligodendrocytes which are specialized to recognize and spirally enwrap multiple axonal segments. In the peripheral nervous system the same function is served by Schwann cells. In both, CNS and PNS myelin, a battery of structural proteins is assembled into the compacted myelin sheath and is required for its normal architecture and long-term stability. However, the myelin sheath is not merely an insulator, but must be considered an “external” glial organelle that remains metabolically coupled to the glial cell body and is involved in a long-lasting bidirectional communication between the axon and its ensheathing glial cell. The molecular cloning of genes encoding myelin-specific membrane proteins and the analysis of a corresponding set of mouse mutants has provided a glimpse at the complex functions of individual myelin proteins in this system. One major component of CNS myelin that has been studied in much detail with the tools of molecular biology, and which is involved in a severe human leukodystrophy (Pelizaeus-Merzbacher disease), is the proteolipid protein (PLP).