Research for transgenic mouse of retinitis pigmentosa with vitamin E deficiency

1)α-生育酚转移蛋白基因敲除小鼠的制备完成了α-生育酚转移蛋白基因敲除小鼠的制备。目前，我们正在利用体感诱发电位和视网膜电图研究中枢神经系统和视网膜的病理及其功能。2）α-生育酚转移蛋白的分布我们用北方杂交技术鉴定了α-生育酚转移蛋白在视网膜、小脑、脊髓中的表达。原位杂交技术证实该蛋白在小脑Bergmann胶质细胞中有局部表达。3）突变型α-生育酚转运蛋白基因患者的尸检研究主要病理表现为视网膜萎缩，后柱的死背型严重变性，神经元包括背根神经节（DRG）细胞内蜡样脂褐素大量积聚。此外，还观察到浦肯野细胞轻度丢失。在被认为是共济失调的主要原因的DRG中，未检测到α-生育酚转移蛋白的表达，并且补充后维生素E的组织浓度增加至正常。因此，我们得出结论，口服补充维生素E应有效地抵消共济失调的进展。

1) Alpha-tocopherol transfer protein knockout mouseWe finished making mouse in which alpha-tocopherol transfer protein gene was deleted. Now, we are investigating pathology of central nervous system, retina, and their functions using somatosensory evoked potentials and retinograms.2) Distribution of alpha-tocopherol transfer proteinWe identify the expression of alpha-tocopherol transfer protein in retina, cerebellum, spinal cord by Northern blot. Furthermore in situ hybridization technique demonstrated that the local expression of the protein in the Bergmann glia in cerebellum. There was no expression in dorsal root ganglia, or peripheral nervous system.3) Investigation on autopsy of patient with mutant alpha-tocopherol transfer protein geneThe major pathological findings were retinal atrophy ; severe degeneration of the dying back-type in the posterior column ; and massive accumulation of ceroid-lipofuscin in neurons including dorsal root ganglion (DRG) cells. In addition, mild loss of Purkinje cells was noted. In the DRG, thought to be mainly responsible for ataxia, no expression of alpha-tocopherol transfer protein was detected, and the tissue concentration of vitamin E increased to normal after supplementation. We therefore concluded that oral supplementation of vitamin E should effectively counteract the progression of ataxia.