PERIPHERAL NEUROPATHY IN MICE TRANSGENIC FOR A HUMAN MDR3 P-GLYCOPROTEIN MINI-GENE

We have generated mice transgenic for a human MDR3 minigene, under con trol 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 d ysmyelination of their peripheral nerves. An extensive dysmyelination in some transgenic strains results in a severe peripheral neuropathy w ith paresis of the hind legs. How expression of the MDR3 transgene cau ses these abnormalities is unknown. The MDR3 gene encodes a large glyc osylated plasma membrane protein with multiple transmembrane spanning domains, which are involved in the translocation of the phospholipid p hosphatidylcholine through the hepatocyte canalicular membrane. The ab ility of the MDR3 P-glycoprotein to alter phospholipid 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 c ell membrane may be sufficient to severely disturb myelination of peri pheral nerves.