Vesico-ureteric reflux and urinary tract development in the Pax21Neu+/−mouse

Murawski, Inga J.; Myburgh, David B.; Favor, Jack; Gupta, Indra R.

doi:10.1152/ajprenal.00221.2007

Cited by 61Pediatric Urology and Nephrology StudiesRenal and related cancersUrological Disorders and Treatments

Vesico-ureteric reflux and urinary tract development in the Pax21Neu+/−mouse

Murawski, Inga J., Myburgh, David B., Favor, Jack, Gupta, Indra R.·2007·American Journal of Physiology-Renal Physiology

DOI 10.1152/ajprenal.00221.2007

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Abstract

Vesico-ureteric reflux (VUR) is a urinary tract abnormality that affects roughly one-third of patients with renal-coloboma syndrome, an autosomal dominant condition caused by a mutation in PAX2. Here, we report that a mouse model with an identical mutation, the Pax2 1Neu+/−mouse, has a 30% incidence of VUR. In VUR, urine flows retrogradely from the bladder to the ureter and is associated with urinary tract infections, hypertension, and renal failure. The propensity to reflux in the Pax2 1Neu+/−mouse is correlated with a shortened intravesical ureter that has lost its oblique angle of entry into the bladder wall compared with wild-type mice. Normally, the kidney and urinary tract develop from the ureteric bud, which grows from a predetermined position on the mesonephric duct. In Pax2 1Neu+/−mice, this position is shifted caudally while surrounding metanephric mesenchyme markers remain unaffected. Mutant offspring from crosses between Pax2 1Neu+/−and Hoxb7/GFP+/−mice have delayed union of the ureter with the bladder and delayed separation of the ureter from the mesonephric duct. These events are not caused by a change in apoptosis within the developing urinary tract. Our results provide the first evidence that VUR may arise from a delay in urinary tract maturation and an explanation for the clinical observation that VUR resolves over time in some affected children.

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Authors: Murawski, I. J., Myburgh, D. B., Favor, J., & Gupta, I. R.
Affiliations: Montreal Children's Hospital (CA)
ORCID: Gupta, Indra R.
Venue: American Journal of Physiology-Renal Physiology
Publisher: American Physiological Society
Published: 2007-11
Volume: 293
Issue: 5
Pages: F1736-F1745
ISSN: 1522-1466 (ISSN-L)
1931-857X
DOI: 10.1152/ajprenal.00221.2007
OpenAlex: W2142392761
Cited by: 61
References: 60
Citations by year: 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 9 · 2014: 3 · 2013: 2 · 2012: 4
FWCI: 4.15
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Renal Physiology (publishedVersion)
PubMed (publishedVersion)
Funders: Kidney Foundation of Canada
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pediatric Urology and Nephrology Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
Health Sciences › Medicine › Urology › Urological Disorders and Treatments
Keywords: vesicoureteral reflux, PAX2, renal coloboma syndrome, urinary tract development, ureteric bud, mesonephric duct, HOXB7, urinary tract infection, mouse model
MeSH terms: Roundabout Proteins, Animals, Urinary Bladder, Disease Models, Animal, Female, Kidney, Male, Mice, Mutant Strains, Mutation, Organ Size, Receptors, Immunologic, Ureter, Urinary Tract, Vesico-Ureteral Reflux, Gene Expression, Incidence, Sex Distribution, Embryonic Development, Glial Cell Line-Derived Neurotrophic Factor, Mice, PAX2 Transcription Factor

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Vesico-ureteric reflux and urinary tract development in the Pax21Neu+/−mouse

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