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Updated: Aug 22, 2026
An Immature Murine Model of Reversible Unilateral Ureteral Obstruction
Published on: April 4, 2025
Overexpression of RET leads to vesicoureteric reflux in mice
O H Yu1, I J Murawski, D B Myburgh
1Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
Abstract:
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.
Insights
Overexpression of RET in mice leads to urinary tract abnormalities, specifically vesicoureteric reflux (VUR). This transgenic model provides insights into VUR development during kidney and urinary tract formation.
Area of Science:
- Developmental Biology
- Urology
- Genetics
Background:
- RET, a tyrosine kinase receptor, is crucial for kidney and urinary tract development.
- Abnormal RET signaling can lead to congenital urinary tract malformations.
- Vesicoureteric reflux (VUR) is a significant urinary tract abnormality with potential for kidney damage.
Purpose of the Study:
- To investigate the role of RET overexpression in urinary tract development and its association with VUR.
- To characterize the anatomical and developmental basis for VUR in the HoxB7/Ret transgenic mouse model.
- To explore the transient nature of VUR during normal urinary tract development.
Main Methods:
- Utilized HoxB7/Ret transgenic mice with overexpressed RET.
- Assessed VUR in vitro by injecting methylene blue into bladders of postnatal and embryonic mice.
- Measured the length of the intravesical ureteral tunnel.
- Examined the caudal exit point of the ureteric bud from the mesonephric duct.
Main Results:
- HoxB7/Ret mice exhibited a significantly higher incidence of VUR at postnatal day 1 (30%) compared to wild-type mice (4%).
- Shorter intravesical ureteral tunnel length was observed in HoxB7/Ret mice, correlating with increased VUR.
- Abnormal caudal positioning of the ureteric bud in HoxB7/Ret embryos at embryonic day 11 predisposed to VUR.
- High VUR frequencies were noted in both wild-type and HoxB7/Ret mice at embryonic day 17, suggesting transient reflux during development.
Conclusions:
- Overexpression of RET in the HoxB7/Ret mouse model delays distal ureter maturation, leading to postnatal VUR.
- The HoxB7/Ret mouse serves as a valuable model for studying the mechanisms underlying VUR.
- Transient VUR may be a normal occurrence during urinary tract development before complete ureteral insertion into the bladder.
