vesicoureteral reflux and other urinary tract malformations in mice compound heterozygous for pax2 and emx2膀胱输尿管的回流和其他老鼠尿路畸形为我们和emx2复合杂合的.pdfVIP

Vesicoureteral Reflux and Other Urinary Tract Malformations in Mice Compound Heterozygous for Pax2 and Emx2 1 1 2 3 2 1 Sami K. Boualia , Yaned Gaitan , Inga Murawski , Robert Nadon , Indra R. Gupta , Maxime Bouchard * 1 Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada, 2 Department of Pediatrics and Department of Human Genetics, McGill University, Montreal, Quebec, Canada, 3 McGill University and Genome Quebec Innovation Centre, McGill University, Montreal, Quebec, Canada Abstract Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. This disease group includes a spectrum of urinary tract defects including vesicoureteral reflux, duplex kidneys and other developmental defects that can be found alone or in combination. To identify new regulators of CAKUT, we tested the genetic cooperativity between several key regulators of urogenital system development in mice. We found a high incidence of urinary tract anomalies in Pax2;Emx2 compound heterozygous mice that are not found in single heterozygous mice. Pax2+/ 2 +/ 2 ;Emx2 mice harbor duplex systems associated with urinary tract obstruction, bifid ureter and a high penetrance of vesicoureteral reflux. Remarkably, most compound heterozygous mice refluxed at low intravesical pressure. Early analysis of Pax2+/ 2 +/ 2 ;Emx2 embryos point to ureter budding defects as the primary cause of urinary tract anomalies. We additionally establish Pax2 as a direct regulator of Emx2 expression in the Wolffian duct. Together, these results identify a haploinsu