MOLECULAR ANALYSIS OF SPONTANEOUS GLOMERULOSCLEROSIS IN OS/+ MICE, A MODEL WITH REDUCED NEPHRON MASS
MOLECULAR ANALYSIS OF SPONTANEOUS GLOMERULOSCLEROSIS IN OS/+ MICE, A MODEL WITH REDUCED NEPHRON MASS
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DOI：
10.1152/ajprenal.1995.269.2.f266
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发表时间：
1995-08-01
期刊：
影响因子：
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通讯作者：
STRIKER, LJ
中科院分区：
文献类型：
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作者：
HE, CJ;ZALUPS, RK;STRIKER, LJ
少并趾小鼠（ROP Os/+）是一种辐射诱导的突变株，肾小球数量减少，肾小球大小增加。我们发现他们患上了肾小球硬化。在3个月时，光镜下，ROP Os/+小鼠有弥漫性系膜扩张，而+/+小鼠没有。电镜形态测量显示系膜面积增加两倍，但肾小球基底层厚度未见变化。肾小球平均体积增加1.8倍。细胞数量和胸腺嘧啶标记指数分别提高1.3倍和2.4倍。免疫荧光显微镜观察肾小球IV型胶原蛋白和腱腱素含量升高，而层粘连蛋白含量未见升高。通过竞争性逆转录-聚合酶链反应测定微解剖肾小球的mRNA水平，并校正细胞数量。α(1)-链型IV型胶原蛋白和腱蛋白mRNA水平分别增加3.2倍和1.8倍，而层粘连蛋白B1 mRNA水平则没有变化。72kda胶原酶rnRNA水平增加1.6倍。转化生长因子- β 1 mRNA水平升高1.8倍，但血小板源性生长因子- β 1 mRNA水平保持正常。这是先天性肾元减少模型中肾小球分子和细胞变化的首次分析。
Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diffuse mesangial expansion by light microscopy, whereas their +/+ littermates did not. Electron microscopic morphometry revealed a twofold increase in mesangial areas but no changes in the thickness of glomerular basal laminae. Mean glomerular volume was increased 1.8-fold. Cell number and thymidine labeling index were increased 1.3- and 2.4-fold, respectively. The amount of glomerular type IV collagen and tenascin but not laminin was increased by immunofluorescence microscopy. mRNA levels in microdissected glomeruli were measured by competitive reverse transcription-polymerase chain reaction and corrected for cell number. alpha(1)-Chain type IV collagen and tenascin mRNAs were increased 3.2-fold and 1.8-fold, whereas laminin B1 mRNA levels were not. The levels of 72-kDa collagenase rnRNA were increased 1.6-fold. Transforming growth factor-beta 1 mRNA levels were elevated 1.8 fold, but platelet-derived growth factor-beta 1 mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of congenital nephron reduction.