title: Peripheral neuropathy in mice transgenic for a human MDR3 P-glycoprotein mini-gene.
abstract: We have generated mice transgenic for a human MDR3 mini-gene, under control of a hamster vimentin promoter. Expression of the MDR3 transgene was found in mesenchymal tissues, peripheral nerves, and the eye lens. These MDR3 transgenic mice have a slowed motor nerve conduction and dysmyelination of their peripheral nerves. An extensive dysmyelination in some transgenic strains results in a severe peripheral neuropathy with paresis of the hind legs. How expression of the MDR3 transgene causes these abnormalities is unknown. The MDR3 gene encodes a large glycosylated plasma membrane protein with multiple transmembrane spanning domains, which are involved in the translocation of the phospholipid phosphatidylcholine through the hepatocyte canalicular membrane. The ability of the MDR3 P-glycoprotein to alter phsopholipid distribution in the plasma membrane of Schwann cells may cause the damage. It is also possible, however, that the presence of a large glycoprotein in the cell membrane may be sufficient to severely disturb myelination of peripheral nerves.
authors.affiliation: The Netherlands Cancer Institute, Division of Molecular Biology, Amsterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Smit
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: J E
authors.initials: JE
authors.lastname: Hoogendijk
authors.forename: G H
authors.initials: GH
authors.lastname: Jansen
authors.forename: M A
authors.initials: MA
authors.lastname: van der Valk
authors.forename: A H
authors.initials: AH
authors.lastname: Schinkel
authors.forename: A J
authors.initials: AJ
authors.lastname: Berns
authors.forename: D
authors.initials: D
authors.lastname: Acton
authors.forename: K
authors.initials: K
authors.lastname: Nooter
authors.forename: H
authors.initials: H
authors.lastname: Burger
authors.forename: S J
authors.initials: SJ
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Borst
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1