Progressive segregation of unmyelinated axons in peripheral nerves, myelinalterations in the CNS, and cyst formation in the kidneys of myelin and lymphocyte protein-overexpressing mice

Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid tha t is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical me mbranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid-enriched memb rane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical anal ysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wil dtype animals, indicating correct spatial regulation of the transgene. Phen otypically, MAL overexpression led to progressive dissociation of unmyelina ted axons from bundles in the PNS, a tendency to hypomyelination and aberra nt myelin formation in the CNS, and the formation of large cysts in the tub ular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells , oligodendrocytes, and kidney epithelial cells.