Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men
Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men
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DOI：
10.1016/s1097-2765(00)80169-0
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发表时间：
1999-01-01
期刊：
影响因子：
16
通讯作者：
Ichikawa, L
中科院分区：
文献类型：
--
作者：
Nishimura, H;Yerkes, E;Ichikawa, L
血管紧张素2型受体基因无效突变小鼠表现出先天性肾脏和泌尿道异常（CAKUT）。小鼠CAKUT的各种特征令人印象深刻地模仿人类CAKUT。在两个独立的队列中对人类2型受体（AGTR 2）基因的研究发现，CAKUT与内含子1的lactobranchpoint基序内的核苷酸转换之间存在显著关联，这干扰了AGTR 2 mRNA剪接效率。因此，AGTR2对肾脏和泌尿道系统具有重要的个体发育作用。研究表明，CAKUT的建立之前，在关键的个体发育事件期间，从输尿管出芽到肾脏和输尿管的扩张生长，泌尿道周围未分化的间充质细胞的延迟凋亡。
Angiotensin type 2 receptor gene null mutant mice display congenital anomalies of the kidney and urinary tract (CAKUT). Various features of mouse CAKUT impressively mimic human CAKUT. Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system. Studies revealed that the establishment of CAKUT is preceded by delayed apoptosis of undifferentiated mesenchymal cells surrounding the urinary tract during key ontogenic events, from the ureteral budding to the expansive growth of the kidney and ureter.