Role of the angiotensin receptor in the development of the mammalian kidney and urinary tract.
Recent gene targeting and pharmacological studies have shown that the renin-angiotensin system is essential for the development of the mammalian kidney and urinary tract system. We have generated mutant mice carrying a targeted null mutation of the angiotensin type 1 receptor (AT1) or type 2 receptor (AT2) gene. Analyses of these two mutant mice revealed that both mutants have a distinct phenotype in the kidney and urinary tract system. Thus, some AT2 null mutants (Agtr2 -/Y) show anomalies that mimic human congenital anomalies of the kidney and urinary tract as a result of a defect in the in utero organogenesis of the excretory system, while AT1 null mutants (Agtr1 -/-) exhibit hydronephrosis due to a defective development of the urinary peristaltic machinery during the perinatal period. In this review, we discuss chronologically from embryos to adults how the angiotensin receptors regulate the morphogenesis of the excretory system.
Miyazaki
Y
Y
Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan.
Ichikawa
I
I
D000809:Angiotensins / Q000502:physiology; D000818:Animals; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000254:growth & development*; D008322:Mammals; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*; D014551:Urinary Tract / Q000002:abnormalities / Q000254:growth & development*
D000809:Angiotensins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin