Bladder-Ureter Integration and Vesicouretal Reflux

Vesicouretal reflux is a common urologic defect caused by incorrect flow of urine from the bladder to the kidneys causing expansion of the ureter and kidney damage.  The Hoxa13 mutant mouse models this defect.  A comparative analysis of genes expressed in Hoxa13 heterozygous control (+/-) and homozygous mutant (-/-) mice using Affymetrix microarrays and ChIP-seq have identified several candidate genes we are currently investigating for a role in bladder/ureter integration and direct regulation by HOXA13.

Bladder-Ureter integration

Developmental analysis of ureter bladder integration reveals an absence of ureter integration into the bladder wall of the Hoxa13 mutant embryo.

Bladder-Ureter Integration

Wild type (left panel) and Hoxa13 mutant (right panel) littermates.  Note ureter and kidney damage (arrows) as a consequence of vesicouretal reflux caused by the failure of the ureter to integrate into the bladder wall during development.