FORMATION AND MAINTENANCE OF THE MYELIN SHEATH IN THE PERIPHERAL-NERVE - ROLES OF CELL-ADHESION MOLECULES AND THE GAP JUNCTION PROTEIN CONNEXIN-32

Based on previous in vitro studies, the cell adhesion molecules L1, N- CAM, MAG, and P0, which all belong to the immunoglobulin (Ig)-superfam ily, have been suggested to mediate myelin formation in the peripheral nervous system. Unexpectedly, studies in mice deficient for the corre sponding molecules revealed that on:Ly PO plays pivotal roles during t he formation of peripheral nerve myelin in vivo, while L1-, N-CAM-, an d MAG-deficient mice develop myelin of normal ultrastructure. However, MAG turned out to be important for the maintenance of myelin, as refl ected by degeneration of myelin and axons in MAG-deficient mice older than 6 months. The MAG-mediated maintenance of myelin is backed up by N-CAM, since mice deficient in both MAG and N-CAM show an earlier and more prominent myelin degeneration than MAG single mutants. Another pe ripheral nerve component involved in the maintenance of myelinated fib ers is connexin 32 (Cx32), a gap junction channel protein that does no t belong to the Ig-superfamily. Mice deficient in Cx32 initially form normal myelin, which then develops blown-up periaxonal collars and abn ormally shaped non-compacted regions followed by myelin and axonal deg eneration. Our findings strongly support the view that very few myelin components are necessary for myelin formation whereas the maintenance of myelin is much more sensitive to molecular alterations. In additio n, it became evident that myelin molecules can fulfill functionally ov erlapping roles that ensure that myelination takes place even under co nditions in which there is a deficiency in the normal molecular compon ents of myelin. Microsc. Res. Tech. 41:403-425, 1998. (C) 1998 Wiley-L iss, Inc.