High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma

David Hains, Sunder Sims-Lucas, Ashley Carpenter, Monalee Saha, Inga Murawski, Kayle Kish, Indra Gupta, Kirk McHugh, Carlton M. Bates

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Abstract

Purpose: Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2Mes-/-) have ureteral bud induction abnormalities. We determined whether Fgfr2Mes-/- mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. Materials and Methods: We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3-dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. Results: Compared with controls Fgfr2Mes-/- embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2Mes-/- mice. Postnatal Fgfr2Mes-/- mutants had a high rate of vesicoureteral reflux compared with controls (47.4% vs 4.0%, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2Mes-/- kidneys compared with that in controls but not statistically different in ureters or bladders. Conclusions: Fgfr2Mes-/- mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis.

Original languageEnglish (US)
Pages (from-to)2077-2084
Number of pages8
JournalJournal of Urology
Volume183
Issue number5
DOIs
StatePublished - May 1 2010

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Vesico-Ureteral Reflux
Mesoderm
Ureter
Urinary Bladder
Kidney
Incidence
Embryonic Structures
Apoptosis
Urinary Tract
In Situ Hybridization
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Hains, D., Sims-Lucas, S., Carpenter, A., Saha, M., Murawski, I., Kish, K., ... Bates, C. M. (2010). High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma. Journal of Urology, 183(5), 2077-2084. https://doi.org/10.1016/j.juro.2009.12.095

High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma. / Hains, David; Sims-Lucas, Sunder; Carpenter, Ashley; Saha, Monalee; Murawski, Inga; Kish, Kayle; Gupta, Indra; McHugh, Kirk; Bates, Carlton M.

In: Journal of Urology, Vol. 183, No. 5, 01.05.2010, p. 2077-2084.

Research output: Contribution to journalArticle

Hains, D, Sims-Lucas, S, Carpenter, A, Saha, M, Murawski, I, Kish, K, Gupta, I, McHugh, K & Bates, CM 2010, 'High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma', Journal of Urology, vol. 183, no. 5, pp. 2077-2084. https://doi.org/10.1016/j.juro.2009.12.095
Hains, David ; Sims-Lucas, Sunder ; Carpenter, Ashley ; Saha, Monalee ; Murawski, Inga ; Kish, Kayle ; Gupta, Indra ; McHugh, Kirk ; Bates, Carlton M. / High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma. In: Journal of Urology. 2010 ; Vol. 183, No. 5. pp. 2077-2084.
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abstract = "Purpose: Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2Mes-/-) have ureteral bud induction abnormalities. We determined whether Fgfr2Mes-/- mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. Materials and Methods: We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3-dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. Results: Compared with controls Fgfr2Mes-/- embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2Mes-/- mice. Postnatal Fgfr2Mes-/- mutants had a high rate of vesicoureteral reflux compared with controls (47.4{\%} vs 4.0{\%}, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2Mes-/- kidneys compared with that in controls but not statistically different in ureters or bladders. Conclusions: Fgfr2Mes-/- mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis.",
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T1 - High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma

AU - Hains, David

AU - Sims-Lucas, Sunder

AU - Carpenter, Ashley

AU - Saha, Monalee

AU - Murawski, Inga

AU - Kish, Kayle

AU - Gupta, Indra

AU - McHugh, Kirk

AU - Bates, Carlton M.

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N2 - Purpose: Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2Mes-/-) have ureteral bud induction abnormalities. We determined whether Fgfr2Mes-/- mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. Materials and Methods: We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3-dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. Results: Compared with controls Fgfr2Mes-/- embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2Mes-/- mice. Postnatal Fgfr2Mes-/- mutants had a high rate of vesicoureteral reflux compared with controls (47.4% vs 4.0%, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2Mes-/- kidneys compared with that in controls but not statistically different in ureters or bladders. Conclusions: Fgfr2Mes-/- mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis.

AB - Purpose: Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2Mes-/-) have ureteral bud induction abnormalities. We determined whether Fgfr2Mes-/- mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. Materials and Methods: We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3-dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. Results: Compared with controls Fgfr2Mes-/- embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2Mes-/- mice. Postnatal Fgfr2Mes-/- mutants had a high rate of vesicoureteral reflux compared with controls (47.4% vs 4.0%, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2Mes-/- kidneys compared with that in controls but not statistically different in ureters or bladders. Conclusions: Fgfr2Mes-/- mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis.

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