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dc.contributor.authorRoberts, Neil A.
dc.contributor.authorHilton, Emma N.
dc.contributor.authorLopes, Filipa M.
dc.contributor.authorSingh, Subir
dc.contributor.authorRandles, Michael J.
dc.contributor.authorGardiner, Natalie J.
dc.contributor.authorChopra, Karl
dc.contributor.authorColetta, Riccardo
dc.contributor.authorBajwa, Zunera
dc.contributor.authorHall, Robert J.
dc.contributor.authorYue, Wyatt W.
dc.contributor.authorSchaefer, Franz
dc.contributor.authorWeber, Stefanie
dc.contributor.authorHenriksson, Roger
dc.contributor.authorStuart, Helen M.
dc.contributor.authorHedman, Håkan
dc.contributor.authorNewman, William G.
dc.contributor.authorWoolf, Adrian S.
dc.date.accessioned2022-08-04T12:55:59Z
dc.date.available2022-08-04T12:55:59Z
dc.date.issued2019-03-08
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/627066/1-s2.0-S0085253819300377-main.pdf?sequence=1
dc.identifier.citationRoberts, N. A., Hilton, E. N., Lopes, F. M., Singh, S., Randles, M. J., Gardiner, N. J., Chopra, K., Coletta, R., Bajwa, Z., Hall, R. J., Yue, W. W., Schaefer, F., Weber, S., Henriksson, R., Stuart, H. M., Hedman, H., Newman, W. G., & Woolf, A. S. (2019). Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder. Kidney International, 95(5), 1138-1152. https://doi.org/10.1016/j.kint.2018.11.040en_US
dc.identifier.issn0085-2538
dc.identifier.doi10.1016/j.kint.2018.11.040
dc.identifier.urihttp://hdl.handle.net/10034/627066
dc.description.abstractMutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.en_US
dc.publisherElsevieren_US
dc.relation.urlhttps://www.kidney-international.org/article/S0085-2538(19)30037-7/fulltext#%20en_US
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/30885509/en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.subjectautonomicen_US
dc.subjectgangliaen_US
dc.subjectgeneen_US
dc.subjectmouseen_US
dc.subjecturinationen_US
dc.titleLrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladderen_US
dc.typeArticleen_US
dc.identifier.eissn1523-1755en_US
dc.contributor.departmentUniversity of Manchester; De Montfort University; University of Oxford; University Hospital of Heidelberg; University-Children’s Hospital Marburg; Umeå University; University of Chesteren_US
dc.identifier.journalKidney Internationalen_US
or.grant.openaccessYesen_US
rioxxterms.funderMR/L002744/1en_US
rioxxterms.identifier.projectMR/L002744/1en_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.kint.2018.11.040en_US
dcterms.dateAccepted2018-11-21
rioxxterms.publicationdate2019-03-08
dc.date.deposited2022-08-04en_US
dc.indentifier.issn0085-2538en_US


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