Montreal Children's Hospital, 2300 Tupper St., Montreal, Quebec, Canada

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Vesico-ureteric reflux (VUR) is a urinary tract abnormality that affects roughly one-third of patients with renal-coloboma syndrome, an autosomal dominant condition caused by a mutation in PAX2. Here, we report that a mouse model with an identical mutation, the Pax2(1Neu+/-) mouse, has a 30% incidence of VUR. In VUR, urine flows retrogradely from the bladder to the ureter and is associated with urinary tract infections, hypertension, and renal failure. The propensity to reflux in the Pax2(1Neu+/-) mouse is correlated with a shortened intravesical ureter that has lost its oblique angle of entry into the bladder wall compared with wild-type mice. Normally, the kidney and urinary tract develop from the ureteric bud, which grows from a predetermined position on the mesonephric duct. In Pax2(1Neu+/-) mice, this position is shifted caudally while surrounding metanephric mesenchyme markers remain unaffected. Mutant offspring from crosses between Pax2(1Neu+/-) and Hoxb7/GFP(+/-) mice have delayed union of the ureter with the bladder and delayed separation of the ureter from the mesonephric duct. These events are not caused by a change in apoptosis within the developing urinary tract. Our results provide the first evidence that VUR may arise from a delay in urinary tract maturation and an explanation for the clinical observation that VUR resolves over time in some affected children.

Written by
Murawski IJ, Myburgh DB, Favor J, Gupta IR.

Reference
Am J Physiol Renal Physiol. 2007 Nov;293(5):F1736-45. Epub 2007 Sep 19

PubMed Abstract
PMID:17881463

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