title: 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.
abstract: 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.
authors.affiliation: Brain Research Institute, Department of Neuromorphology, University of Zürich and Swiss Federal Institute of Technology, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Frank
authors.forename: S
authors.initials: S
authors.lastname: Atanasoski
authors.forename: S
authors.initials: S
authors.lastname: Sancho
authors.forename: J P
authors.initials: JP
authors.lastname: Magyar
authors.forename: T
authors.initials: T
authors.lastname: Rülicke
authors.forename: M E
authors.initials: ME
authors.lastname: Schwab
authors.forename: U
authors.initials: U
authors.lastname: Suter
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000818:Animals; D001284:Atrophy; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D004847:Epithelial Cells / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D018628:Gene Dosage; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C569027:Mal protein, mouse; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids