Perevozchikov A P, Vaĭsman B L, Sorokin A V, Kuryshev V Iu, Vorob'ev E V, Dozortsev D I, Konovalov G V, Otellin V A, Dizhe E B, Missiul' B V
Mol Biol (Mosk). 1993 Jan-Feb;27(1):24-37.
Two transgenic rabbits which carried human apolipoprotein A-1 (apo A-1) cDNA under mouse ribosomal protein L/32 promoter were obtained. The effectiveness of transgenosis was confirmed by DNA dot/blot and Southern blot hybridizations. Both transgenic animals had paralyses of fore or fore and high limbs. Electron microscopy demonstrated distinct degradative changes of those parts of spinal cord which were responsible for leg skeletal muscle innervation. RNA dot/blot hybridization showed transgene expression in liver and brain but not in kidney of adult transgenic animal. However, analysis of blood serum lipids and immunochemical determinations gave no indications of the presence of human apo A-1 in adult transgenic rabbit. The data obtained allow us to suggest that the observed pathology was due to interference of native and foreign protein products of apo A-1 gene expression in CNS in the course of embryo development. This suggestion was supported by results of in situ hybridization of 5- and 9-week human embryo sections with apo A-1 cDNA, showing effective expression of apo A-1 gene in neural cells of CNS. Results of transgenosis may be viewed as modeling of the neurological syndrome of human Tangier disease.
获得了两只在小鼠核糖体蛋白L/32启动子控制下携带人载脂蛋白A-1（apo A-1）cDNA的转基因兔。通过DNA点杂交/印迹和Southern印迹杂交证实了转基因的有效性。两只转基因动物均出现前肢或前肢及后肢麻痹。电子显微镜显示，脊髓中负责腿部骨骼肌神经支配的部分有明显的降解变化。RNA点杂交/印迹显示成年转基因动物肝脏和脑中存在转基因表达，但肾脏中没有。然而，血清脂质分析和免疫化学测定未显示成年转基因兔中存在人apo A-1。所获得的数据使我们认为，观察到的病理学现象是由于apo A-1基因表达的天然和外源蛋白质产物在胚胎发育过程中对中枢神经系统产生干扰所致。5周和9周人胚胎切片与apo A-1 cDNA的原位杂交结果支持了这一观点，显示apo A-1基因在中枢神经系统神经细胞中有效表达。转基因结果可被视为人类Tangier病神经综合征的模型。
