Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans
Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans
复制标题
DOI：
10.1111/j.1365-2443.2004.00805.x
复制
发表时间：
2004-12-01
期刊：
影响因子：
2.1
通讯作者：
Yokota, Y
中科院分区：
文献类型：
--
作者：
Aoki, Y;Mori, S;Yokota, Y
先天性肾积水是人类最常见的异常之一，可能导致儿童肾功能衰竭。一半的病例是由于肾盂输尿管连接部（UPJ）梗阻。在这里，我们报告说，小鼠缺乏Id 2，抑制剂的碱性螺旋-环-螺旋（bHLH）转录因子，表现出肾盂积水模仿人类病例的特点，如单侧性和男性优势。甚至在Id 2（+/-）小鼠中也发现肾积水。Id 2（-/-）组男性占67.2%，Id 2（+/-）组男性占48.8%，Id 2（-/-）组女性占28.0%，Id 2（+/-）组女性占20.0%。输尿管在UPJ处的扭曲或高位插入是经常观察到的，这些形态学变化在胚胎发育后期是明显的。组织学上，肌肉层，其中Id 2是正常表达，是肥大和/或不规则的UPJ。此外，基因表达分析表明，BMP 4（骨形态发生蛋白4），这是已知的参与肾积水的发展，似乎作为一个上游因子的Id 2的功能。因此，我们的结果提出了Id 2是导致人类肾积水发病机制的基因的可能性。
Congenital hydronephrosis is one of the most common anomalies found in humans and may cause renal failure in childhood. Half of the cases are due to obstruction at the ureteropelvic junction (UPJ). Here we report that mice lacking Id2, an inhibitor of basic helix-loop-helix (bHLH) transcription factors, exhibit hydronephrosis mimicking the characteristics of human cases such as unilaterality and male preponderance. Hydronephrosis was found even in Id2(+/-) mice. The penetrance was 67.2% in Id2(-/-) males, 48.8% in Id2(+/-) males, 28.0% in Id2(-/-) females and 20.0% in Id2(+/-) females. Distortion or high insertion of the ureter at the UPJ was frequently observed and these morphological changes were evident in late embryogenesis. Histologically, the muscle layer, where Id2 is normally expressed, was hypertrophic and/or irregular at the UPJ. Furthermore, gene expression analysis suggested that BMP4 (bone morphogenetic protein 4), which is known to be involved in the development of hydronephrosis, appears to function as an upstream factor of Id2. Our results thus raise the possibility that Id2 is a gene responsible for the pathogenesis of hydronephrosis in man.