title: From gene discovery to new biological mechanisms: heparanases and congenital urinary bladder disease.
abstract: We present a scientific investigation into the pathogenesis of a urinary bladder disease. The disease in question is called urofacial syndrome (UFS), a congenital condition inherited in an autosomal recessive manner. UFS features incomplete urinary bladder emptying and vesicoureteric reflux, with a high risk of recurrent urosepsis and end-stage renal disease. The story starts from a human genomic perspective, then proceeds through experiments that seek to determine the roles of the implicated molecules in embryonic frogs and newborn mice. A future aim would be to use such biological knowledge to intelligently choose novel therapies for UFS. We focus on heparanase proteins and the peripheral nervous system, molecules and tissues that appear to be key players in the pathogenesis of UFS and therefore must also be critical for functional differentiation of healthy bladders. These considerations allow the envisioning of novel biological treatments, although the potential difficulties of targeting the developing bladder in vivo should not be underestimated.
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Royal Manchester Children's Hospital, Manchester, UK.
authors: Neil A
authors: NA
authors: Roberts
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Royal Manchester Children's Hospital, Manchester, UK.
authors: Emma N
authors: EN
authors: Hilton
authors: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Royal Manchester Children's Hospital, Manchester, UK.
authors: Adrian S
authors: AS
authors: Woolf
mesh_terms: D000818:Animals; D056726:Genetic Association Studies; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics*; D001745:Urinary Bladder Diseases / Q000151:congenital* / Q000201:enzymology / Q000235:genetics*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: HPSE; LRIG; growth; neuron; receptor; signalling