HIV-ASSOCIATED NEPHROPATHY IN TRANSGENIC MICE EXPRESSING HIV-1 GENES
HIV-ASSOCIATED NEPHROPATHY IN TRANSGENIC MICE EXPRESSING HIV-1 GENES
复制标题
DOI：
10.1016/0042-6822(91)90759-5
复制
发表时间：
1991-11-01
期刊：
影响因子：
3.7
通讯作者：
NOTKINS, AL
中科院分区：
文献类型：
--
作者：
DICKIE, P;FELSER, J;NOTKINS, AL
转基因小鼠产生的副本有缺陷的艾滋病毒前病毒。来自三个独立来源的小鼠系的转基因后代表现出与蛋白尿相关的肾病、高死亡率以及肾脏中HIV特异性基因表达。肾脏的早期组织病理学病变为局灶性肾小球硬化。濒死动物出现弥漫性肾小球硬化，伴明显的微囊肾小管扩张、肾小管上皮变性和间质性肾炎。电子显微镜检查显示与肾小球硬化症一致的超微结构特征：内脏上皮足突消失，系膜细胞基质增加。转基因小鼠在包括肾脏在内的几种组织中表达了6-、4.3-和2-kb的HIV特异性RNA和HIV相关多肽。免疫细胞染色显示，在受影响的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和人类HIV相关肾病具有相似的特征。
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.