mutation caused kidney hypoplasia and defective ureter-bladder connections in mice.

Limited genetic factors were uncovered for the development of congenital anomalies of the kidney and urinary tract (CAKUT). We previously reported that a Holliday junction resolvase was essential for early metanephric development in mice. This comprehensive follow-up study focused on the roles of in late metanephric development. We found that mutation impaired the late development of both kidney and urinary tract. and kidney primordia culture confirmed decreased ureteric bud branching in mutants, which consequently caused hypoplasia. We also observed abnormal urinary tract development. Programmed apoptosis at the end of nephric duct disappeared in mutants, which caused abnormal ureter-bladder connections, leading to vesicoureteral reflux (VUR) or ureterovesical junction obstruction (UVJO). Mechanistically, RNA-seq analysis proved that mutation impaired the expression of multiple regulatory genes for the metanephric development, including . Taken together, our study provides more insight into the roles of in the development of the kidney and urinary tract, which may have potential clinical significance in the treatment and/or prevention of CAKUT.