FVB mouse genotype confers susceptibility to OVE26 diabetic albuminuria.
FVB mouse genotype confers susceptibility to OVE26 diabetic albuminuria.
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DOI：
10.1152/ajprenal.00018.2010
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发表时间：
2010-07
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影响因子：
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通讯作者：
Jianxiang Xu;Yun Huang;Fenge Li;S. Zheng;P. Epstein
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作者：
Jianxiang Xu;Yun Huang;Fenge Li;S. Zheng;P. Epstein
近交系FVB的OVE 26（OVE）糖尿病小鼠是糖尿病肾病的有价值的模型，其在所有糖尿病小鼠模型中排泄最高量的尿白蛋白。将OVE小鼠与C57BL6或DBA2小鼠杂交，F1糖尿病后代的白蛋白尿减少了17倍，但糖尿病没有减少。当比较FVB背景下的OVE小鼠与F1 C57BL6杂交小鼠的肾组织学时，我们发现F1肾脏具有显著较小的肾小球，肾小管中白蛋白积聚少得多，系膜基质扩张减少，间质纤维化减少。对108个OVE阳性的N2后代的蛋白尿进行基因组扫描，发现11号染色体上有一个显著的峰，9号、13号和19号染色体上几乎有显著的峰。11、13或19号染色体上峰的FVB基因型纯合性增加白蛋白尿。9号染色体的纯合性峰减少蛋白尿。染色体11、13和19上的峰的组合同源性使白蛋白尿增加超过12倍，并且占FVB与F1背景的OVE小鼠之间差异的>70%。这些基因座含有对糖尿病蛋白尿易感性重要的序列。
OVE26 (OVE) diabetic mice on the inbred strain FVB are a valuable model of diabetic nephropathy that excretes the highest amount of urine albumin of all diabetic mouse models. Crossing of OVE mice to C57BL6 or DBA2 mice reduced albuminuria 17-fold in F1 diabetic offspring without reducing diabetes. When comparing renal histology of OVE mice on the FVB background to F1 C57BL6 crosses, we found that the F1 kidneys had significantly smaller glomeruli, much less albumin accumulation in tubules, reduced mesangial matrix expansion, and less interstitial fibrosis. A genome scan of 108 OVE-positive N2 offspring for albuminuria revealed one significant peak on chromosome 11 and nearly significant peaks on chromosomes 9, 13, and 19. Homozygosity for the FVB genotype for peaks on chromosomes 11, 13, or 19 increased albuminuria. Homozygosity for the chromosome 9 peak reduced albuminuria. Combined homozyogosity for the peaks on chromosomes 11, 13, and 19 increased albuminuria over 12-fold and accounted for >70% of the difference between OVE mice on the FVB vs. the F1 background. These loci contain sequences important to susceptibility to diabetic albuminuria.