MYELIN AND LYMPHOCYTE PROTEIN (MAL MVP17/VIP17) AND PLASMOLIPIN ARE MEMBERS OF AN EXTENDED GENE FAMILY/

An increasing number of four-transmembrane proteins has been found to be associated with CNS and PNS myelin. Some of these proteins play cru cial roles in the development and maintenance of the nervous system. I n the CNS, proteolipid protein (PLP) is mutated in the myelin disorder Pelizaeus-Merzbacher disease and in spastic paraplegia, while in the PNS, peripheral myelin protein 22 (PMP22) and connexin32 (C x 32) are culprit genes in the most frequent forms of hereditary peripheral neur opathies. Myelin and lymphocyte protein (MAL; also called MVP17 or VIP 17) and plasmolipin are additional tetraspan proteins that are highly expressed by myelinating glial cells. However, little is known about t he role of these proteins in the nervous system. As a prerequisite for functional genetic approaches in the mouse, we have isolated and char acterized a mouse MAL cDNA and the corresponding structural MAL gene. Computer-aided analysis and database searches revealed that MAL belong s to a larger gene family which also includes plasmolipin, BENE and th e expressed sequence tag (EST) H09290. While the overall amino acid se quence identities between mouse MAL and the related proteins are relat ively low (29-37%), the conserved motif -[Q/Y-G-W-V-M-F/Y-V]- which is found at the junction of the first extracellular loop and the second membrane-associated domain serves as a fingerprint for the MAL protein family. Expression analysis of the members of the MAL gene family ind icates widespread expression in various tissues? suggesting a common r ole of these proteins in cell biology. (C) 1997 Elsevier Science B.V.