HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/F1123    most recent 00444.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Yu, O. H. Articles by Gupta, I. R. Search for Related Content PubMed PubMed Citation Articles by Yu, O. H. Articles by Gupta, I. R.

Overexpression of RET leads to vesicoureteric reflux in mice

¹Departments of Pediatrics and ²Human Genetics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada H3H 1P3

Submitted 17 December 2003 ; accepted in final form 18 August 2004

RET, a tyrosine kinase receptor essential for kidney development, has recently been shown to be important for the formation of the urinary tract. When RET is overexpressed in the HoxB7/Ret transgenic mouse, kidneys are small and cystic, and in some of the mice, the ureters are grossly dilated. Here, we report that the observed ureteral dilatation is associated with the urinary tract abnormality vesicoureteric reflux (VUR), in which urine flows retrogradely from the bladder to the ureter. Reflux was determined in vitro by injecting methylene blue into the bladders of HoxB7/Ret and wild-type mice. At postnatal day 1, 30% of HoxB7/Ret mice had VUR compared with 4% of wild-type mice (P < 0.05). The length of the intravesical ureteral tunnel was shorter in HoxB7/Ret mice compared with wild-type mice, on both the right and the left sides (P < 0.05), suggesting a basis for the higher incidence of VUR in these mutants. At embryonic day 11, the ureteric bud was found to exit more caudally from the mesonephric duct in HoxB7/Ret mice, and this may predispose them to VUR (P < 0.05). Wild-type and HoxB7/Ret mice were tested for reflux at embryonic day 17, and both showed a high frequency of VUR (59 and 75%, respectively). These results suggest that VUR may occur transiently during normal urinary tract development before the ureter has completed its insertion into the bladder. In the HoxB7/Ret mouse, overexpression of RET appears to delay the maturation of the distal ureter, resulting in postnatal VUR. The HoxB7/Ret mouse is thus an important model in which to examine how vesicoureteric reflux arises during urinary tract development.

kidney defect; urinary tract defect; ureteric bud

This article has been cited by other articles:

				D. B. Sparrow, S. C. Boyle, R. S. Sams, B. Mazuruk, L. Zhang, G. W. Moeckel, S. L. Dunwoodie, and M. P. de Caestecker Placental Insufficiency Associated with Loss of Cited1 Causes Renal Medullary Dysplasia J. Am. Soc. Nephrol., April 1, 2009; 20(4): 777 - 786. [Abstract] [Full Text] [PDF]

				G. Williams, J. T. Fletcher, S. I. Alexander, and J. C. Craig Vesicoureteral Reflux J. Am. Soc. Nephrol., May 1, 2008; 19(5): 847 - 862. [Abstract] [Full Text] [PDF]

				I. J. Murawski, D. B. Myburgh, J. Favor, and I. R. Gupta Vesico-ureteric reflux and urinary tract development in the Pax21Neu+/ mouse Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1736 - F1745. [Abstract] [Full Text] [PDF]

				R. Viana, E. Batourina, H. Huang, G. R. Dressler, A. Kobayashi, R. R. Behringer, E. Shapiro, T. Hensle, S. Lambert, and C. Mendelsohn The development of the bladder trigone, the center of the anti-reflux mechanism Development, October 15, 2007; 134(20): 3763 - 3769. [Abstract] [Full Text] [PDF]

				K. R. Vats, C. Ishwad, I. Singla, A. Vats, R. Ferrell, D. Ellis, M. Moritz, U. Surti, P. Jayakar, D. R. Frederick, et al. A Locus for Renal Malformations Including Vesico-Ureteric Reflux on Chromosome 13q33-34 J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1158 - 1167. [Abstract] [Full Text] [PDF]