Dickie P, Felser J, Eckhaus M, Bryant J, Silver J, Marinos N, Notkins A L
Laboratory of Oral Medicine, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Virology. 1991 Nov;185(1):109-19. doi: 10.1016/0042-6822(91)90759-5.
Transgenic mice were produced that bore copies of a defective HIV provirus. The transgenic offspring from three independently derived mouse lines manifested renal disease associated with proteinuria, a high mortality rate, and HIV-specific gene expression in the kidney. An early histopathological lesion in the kidney was focal glomerulosclerosis. Moribund animals had diffuse glomerulosclerosis with prominent microcystic tubular dilatation, tubular epithelial degeneration, and interstitial nephritis. Electron microscopy revealed ultrastructural features consistent with the glomerulosclerosis: effacement of the foot processes of visceral epithelium and an increase in mesangial cell matrix. Transgenic mice variably expressed 6-, 4.3-, and 2-kb HIV-specific RNAs and HIV-related polypeptides in several tissues including kidney. Immunocytostaining revealed the presence of HIV-related protein in the glomeruli of affected animals. Glomerulopathy in these transgenic mice and HIV-associated nephropathy in man have similar features.
产生了携带缺陷型HIV前病毒拷贝的转基因小鼠。来自三个独立衍生小鼠品系的转基因后代表现出与蛋白尿相关的肾脏疾病、高死亡率以及肾脏中的HIV特异性基因表达。肾脏早期的组织病理学病变是局灶性肾小球硬化。濒死动物出现弥漫性肾小球硬化，伴有明显的微囊性肾小管扩张、肾小管上皮变性和间质性肾炎。电子显微镜检查显示超微结构特征与肾小球硬化一致：脏层上皮足突消失和系膜细胞基质增加。转基因小鼠在包括肾脏在内的多个组织中可变地表达6kb、4.3kb和2kb的HIV特异性RNA以及HIV相关多肽。免疫细胞化学染色显示受影响动物的肾小球中存在HIV相关蛋白。这些转基因小鼠的肾小球病与人的HIV相关性肾病具有相似特征。
