Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men

Angiotensin type 2 receptor gene null mutant mice display congenital anomal ies of the kidney and urinary tract (CAKUT). Various features of mouse CAKU T impressively mimic human CAKUT. Studies of the human type 2 receptor (AGT R2) gene in two independent cohorts found that a significant association ex ists between CAKUT and a nucleotide transition within the lariat branchpoin t motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary trac t system. Studies revealed that the establishment of CAKUT is preceded by d elayed apoptosis of undifferentiated mesenchymal cells surrounding the urin ary tract during key ontogenic events, from the ureteral budding to the exp ansive growth of the kidney and ureter.