{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T15:01:59Z","timestamp":1760799719880},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:p>To date, over 65 mutations in the gene encoding Cx43 (connexin43) have been linked to the autosomal-dominant disease ODDD (oculodentodigital dysplasia). A subset of these patients experience bladder incontinence which could be due to underlying neurogenic deterioration or aberrant myogenic regulation. BSMCs (bladder smooth muscle cells) from wild-type and two Cx43 mutant lines (Cx43G60S and Cx43I130T) that mimic ODDD exhibit a significant reduction in total Cx43. Dye transfer studies revealed that the G60S mutant was a potent dominant-negative inhibitor of co-expressed Cx43, a property not equally shared by the I130T mutant. BSMCs from both mutant mouse strains were defective in their ability to contract, which is indicative of phenotype changes due to harbouring the Cx43 mutants. Upon stretching, Cx43 levels were significantly elevated in controls and mutants containing BSMCs, but the non-muscle myosin heavy chain A levels were only reduced in cells from control mice. Although the Cx43G60S mutant mice showed no difference in voided urine volume or frequency, the Cx43I130T mice voided less frequently. Thus, similar to the diversity of morbidities seen in ODDD patients, genetically modified mice also display mutation-specific changes in bladder function. Furthermore, although mutant mice have compromised smooth muscle contraction and response to stretch, overriding bladder defects in Cx43I130T mice are likely to be complemented by neurogenic changes.<\/jats:p>","DOI":"10.1042\/bj20130810","type":"journal-article","created":{"date-parts":[[2013,11,18]],"date-time":"2013-11-18T13:33:02Z","timestamp":1384781582000},"page":"441-449","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Myogenic bladder defects in mouse models of human oculodentodigital dysplasia"],"prefix":"10.1042","volume":"457","author":[{"given":"Tao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Simek","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn\u00a0I.","family":"Fishman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale\u00a0W.","family":"Laird","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"},{"name":"Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada, N6A 5C1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2014,1,10]]},"reference":[{"key":"2021112215470980300_B1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pbiomolbio.2007.03.011","article-title":"Connexin channel permeability to cytoplasmic molecules","volume":"94","author":"Harris","year":"2007","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2021112215470980300_B2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrm1072","article-title":"Beyond the gap: functions of unpaired connexon channels","volume":"4","author":"Goodenough","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021112215470980300_B3","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev.bi.65.070196.002355","article-title":"Connexins, connexons, and intercellular communication","volume":"65","author":"Goodenough","year":"1996","journal-title":"Annu. Rev. Biochem."},{"key":"2021112215470980300_B4","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/BJ20051922","article-title":"Life cycle of connexins in health and disease","volume":"394","author":"Laird","year":"2006","journal-title":"Biochem. 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Biol."},{"key":"2021112215470980300_B8","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1093\/carcin\/15.10.2163","article-title":"Increased gap junctional intercellular communication capacity and connexin 43 and 26 expression in rat bladder carcinogenesis","volume":"15","author":"Asamoto","year":"1994","journal-title":"Carcinogenesis"},{"key":"2021112215470980300_B9","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.juro.2012.02.2556","article-title":"\u03b2-Catenin signaling contributes to platelet derived growth factor elicited bladder smooth muscle cell contraction through up-regulation of Cx43 expression","volume":"188","author":"Li","year":"2012","journal-title":"J. Urol."},{"key":"2021112215470980300_B10","doi-asserted-by":"crossref","first-page":"41552","DOI":"10.1074\/jbc.M111.274449","article-title":"Reciprocal regulation between proinflammatory cytokine-induced inducible NO synthase (iNOS) and connexin43\u00a0in bladder smooth muscle cells","volume":"286","author":"Li","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2021112215470980300_B11","doi-asserted-by":"crossref","first-page":"e48897","DOI":"10.1371\/journal.pone.0048897","article-title":"Cellular expression profile for interstitial cells of cajal in bladder: a cell often misidentified as myocyte or myofibroblast","volume":"7","author":"Yu","year":"2012","journal-title":"PLoS One"},{"key":"2021112215470980300_B12","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1242\/dev.02011","article-title":"A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia","volume":"132","author":"Flenniken","year":"2005","journal-title":"Development"},{"key":"2021112215470980300_B13","doi-asserted-by":"crossref","first-page":"20512","DOI":"10.1073\/pnas.0705472105","article-title":"Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia","volume":"104","author":"Kalcheva","year":"2007","journal-title":"Proc. Natl. Acad. Sci. 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Commun."},{"key":"2021112215470980300_B23","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s11255-008-9516-7","article-title":"Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats","volume":"41","author":"Miyazato","year":"2009","journal-title":"Int. Urol. Nephrol."},{"key":"2021112215470980300_B24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/j.1464-410X.2005.05703.x","article-title":"Alterations in connexin expression in the bladder of patients with urge symptoms","volume":"96","author":"Neuhaus","year":"2005","journal-title":"BJU Int."},{"key":"2021112215470980300_B25","doi-asserted-by":"crossref","first-page":"R1241","DOI":"10.1152\/ajpregu.00030.2002","article-title":"Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in\u00a0vivo","volume":"284","author":"Christ","year":"2003","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021112215470980300_B26","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1177\/0883073808317730","article-title":"Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family","volume":"23","author":"Amador","year":"2008","journal-title":"J. Child Neurol."},{"key":"2021112215470980300_B27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/nau.2034","article-title":"A new enzymic method for the isolation and culture of human bladder body smooth muscle cells","volume":"21","author":"Ma","year":"2002","journal-title":"Neurourol. Urodyn."},{"key":"2021112215470980300_B28","doi-asserted-by":"crossref","first-page":"19190","DOI":"10.1074\/jbc.M609653200","article-title":"Differential potency of dominant negative connexin43 mutants in oculodentodigital dysplasia","volume":"282","author":"Gong","year":"2007","journal-title":"J. Biol. 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Res."},{"key":"2021112215470980300_B35","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/nau.20552","article-title":"Voided stain on paper method for analysis of mouse urination","volume":"27","author":"Sugino","year":"2008","journal-title":"Neurourol. Urodyn."},{"key":"2021112215470980300_B36","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.juro.2011.02.018","article-title":"Regulation of connexin 43 by basic fibroblast growth factor in the bladder: transcriptional and behavioral implications","volume":"185","author":"Negoro","year":"2011","journal-title":"J. Urology"},{"key":"2021112215470980300_B37","first-page":"239","article-title":"Intercellular communication and bladder function","volume":"539","author":"Christ","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"2021112215470980300_B38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1042\/BJ20121070","article-title":"The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically-modified mice","volume":"449","author":"Stewart","year":"2012","journal-title":"Biochem. J."},{"key":"2021112215470980300_B39","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1161\/01.RES.0000168369.79972.d2","article-title":"Functional characterization of connexin43 mutations found in patients with oculodentodigital dysplasia","volume":"96","author":"Shibayama","year":"2005","journal-title":"Circ. Res."},{"key":"2021112215470980300_B40","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1006\/excr.2001.5465","article-title":"Connexins 43 and 26 are differentially increased after rat bladder outlet obstruction","volume":"274","author":"Haefliger","year":"2002","journal-title":"Exp. Cell Res."},{"key":"2021112215470980300_B41","doi-asserted-by":"crossref","first-page":"475.e1","DOI":"10.1016\/j.urology.2011.03.029","article-title":"Therapeutic effects of connexin inhibitors on detrusor overactivity induced by bladder outlet obstruction in rats","volume":"78","author":"Kim","year":"2011","journal-title":"Urology"},{"key":"2021112215470980300_B42","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1159\/000189585","article-title":"The expression of connexin 43\u00a0in human kidney and cultured renal cells","volume":"75","author":"Hillis","year":"1997","journal-title":"Nephron"},{"key":"2021112215470980300_B43","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1111\/j.1464-410X.2008.08337.x","article-title":"Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder","volume":"103","author":"Suadicani","year":"2009","journal-title":"BJU Int."},{"key":"2021112215470980300_B44","doi-asserted-by":"crossref","first-page":"F46","DOI":"10.1152\/ajprenal.90207.2008","article-title":"Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle","volume":"297","author":"Imamura","year":"2009","journal-title":"Am. 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