Smit J J, Baas F, Hoogendijk J E, Jansen G H, van der Valk M A, Schinkel A H, Berns A J, Acton D, Nooter K, Burger H, Smith S J, Borst P
The Netherlands Cancer Institute, Division of Molecular Biology, Amsterdam, The Netherlands.
J Neurosci. 1996 Oct 15;16(20):6386-93. doi: 10.1523/JNEUROSCI.16-20-06386.1996.
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.
我们构建了在仓鼠波形蛋白启动子控制下的人MDR3小基因转基因小鼠。在间充质组织、外周神经和晶状体中发现了MDR3转基因的表达。这些MDR3转基因小鼠的运动神经传导减慢，外周神经出现髓鞘形成异常。一些转基因品系中广泛的髓鞘形成异常导致严重的外周神经病变并伴有后腿轻瘫。MDR3转基因的表达如何导致这些异常尚不清楚。MDR3基因编码一种具有多个跨膜结构域的大型糖基化质膜蛋白，这些结构域参与磷脂磷脂酰胆碱通过肝细胞胆小管膜的转运。MDR3 P-糖蛋白改变雪旺氏细胞质膜中磷脂分布的能力可能会造成损害。然而，细胞膜中存在大型糖蛋白也可能足以严重干扰外周神经的髓鞘形成。
