Premium
Progressive Segregation of Unmyelinated Axons in Peripheral Nerves, Myelin Alterations in the CNS, and Cyst Formation in the Kidneys of Myelin and Lymphocyte Protein‐Overexpressing Mice
Author(s) -
Frank Marcus,
Atanasoski Suzana,
Sancho Sara,
Magyar Josef P.,
Rülicke Thomas,
Schwab Martin E.,
Suter Ueli
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751927.x
Subject(s) - myelin , biology , proteolipid protein 1 , genetically modified mouse , microbiology and biotechnology , pathology , transgene , peripheral nervous system , myelin basic protein , central nervous system , neuroscience , biochemistry , gene , medicine
Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes 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 membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular 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.