Angiotensin type II receptor expression and ureteral budding.
OBJECTIVE
Deletion of the angiotensin type II receptor gene (Agtr2) in mice results in a spectrum of urinary tract anomalies similar to that in humans. The mechanism behind this anomalous development is poorly understood. We evaluated Agtr2 expression as it relates to normal and abnormal ureteral budding.


METHODS
A total of 400 wild type mice were inspected at birth for gross evidence of a urinary tract anomaly. In addition, the urinary tracts of 30 wild type embryos were evaluated at 11.0/11.5 and 13.5 weeks of gestation. These embryos were examined for ureteral budding site via section and whole mount in situ hybridization with c-ret probe and Agtr2 expression via in situ hybridization with Agtr2 riboprobe. There were 740 newborn mice homozygous for the null mutation of Agtr2 also evaluated along with 55 angiotensin type II knockout embryos at the aforementioned gestational ages.


RESULTS
All wild type newborn animals were grossly normal. Of the angiotensin type II knockout newborns 23 (3.1%) had gross abnormalities of the urinary tract at birth. The predominant finding was a duplicated collecting system associated with a hydronephrotic upper pole moiety. These duplicated collecting systems fulfilled the Meyer-Weigert law. Interestingly, 25 (59.5%) of the knockout embryos showed abnormal ureteral budding. However, in wild type embryos Agtr2 was expressed at this "ectopic" cranial site between the wolffian duct and metanephric mesenchyme.


CONCLUSIONS
Although not the sole regulator, angiotensin type II receptor expression may have a role in the embryological development of the urinary tract by inhibiting aberrant ureteral budding. A defect in this inhibitory process appears to cause ectopic ureteral budding, and may subsequently lead to renal dysplasia and other congenital anomalies of the kidney and urinary tract.
Oshima
K
K
Department of Pediatric Urology, Vanderbilt Children's Hospital, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Miyazaki
Y
Y
Brock
J W
JW
Adams
M C
MC
Ichikawa
I
I
Pope
J C
JC
D000818:Animals; D000831:Animals, Newborn; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014513:Ureter / Q000002:abnormalities / Q000196:embryology*; D014928:Wolffian Ducts / Q000196:embryology
D011945:Receptors, Angiotensin