Dysfunctional bladder neurophysiology in urofacial syndrome Hpse2 mutant mice

Imerjit Manak, Alison M. Gurney, Karen D. McCloskey, Adrian S. Woolf, Neil A. Roberts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
8 Downloads (Pure)


Aims: Urofacial syndrome (UFS) is an autosomal recessive disease characterized by detrusor contraction against an incompletely dilated outflow tract. This dyssynergia causes dribbling incontinence and incomplete voiding. Around half of individuals with UFS have biallelic mutations of HPSE2 that encodes heparanase 2, a protein found in pelvic ganglia and bladder nerves. Homozygous Hpse2 mutant mice have abnormal patterns of nerves in the bladder body and outflow tract, and also have dysfunctional urinary voiding. We hypothesized that bladder neurophysiology is abnormal Hpse2 mutant mice. Methods: Myography was used to study bladder bodies and outflow tracts isolated from juvenile mice. Myogenic function was analyzed after chemical stimulation or blockade of key receptors. Neurogenic function was assessed by electrical field stimulation (EFS). Muscarinic receptor expression was semi-quantified by Western blot analysis. Results: Nitrergic nerve-mediated relaxation of precontracted mutant outflow tracts was significantly decreased vs littermate controls. The contractile ability of mutant outflow tracts was normal as assessed by KCl and the α1-adrenoceptor agonist phenylephrine. EFS of mutant bladder bodies induced significantly weaker contractions than controls. Conversely, the muscarinic agonist carbachol induced significantly stronger contractions of bladder body than controls. Conclusions: The Hpse2 model of UFS features aberrant bladder neuromuscular physiology. Further work is required to determine whether similar aberrations occur in patients with UFS.

Original languageEnglish
Pages (from-to)1930-1938
Number of pages9
JournalNeurourology and Urodynamics
Issue number7
Publication statusPublished - 01 Sep 2020

Bibliographical note

Funding Information:
We acknowledge funding from: Kidney Research UK (Non‐Clinical Training Fellowship PDF_005_20151126 and Intercalated Degree Funding ID_012_20180330; and from the Medical Research Council (Project grants MR/L002744/1 and MR/T016809/1).

Publisher Copyright:
© 2020 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals LLC

Copyright 2020 Elsevier B.V., All rights reserved.


  • bladder dysfunction
  • genetic disease
  • mouse model
  • neuropathy
  • urination

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology


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