{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:13Z","timestamp":1787028613249,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,7,10]],"date-time":"2015-07-10T00:00:00Z","timestamp":1436486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Turner syndrome (TS), most frequently caused by X-monosomy (45,X), is characterized in part by cardiovascular abnormalities, including aortopathy and bicuspid aortic valve (BAV). There is a need for animal models that recapitulate the cardiovascular manifestations of TS. Extracellular matrix (ECM) organization and morphometrics of the aortic valve and proximal aorta were examined in adult 39,XO mice (where the parental origin of the single X was paternal (39,XPO) or maternal (39,XMO)) and 40,XX controls. Aortic valve morphology was normal (tricuspid) in all of the 39,XPO and 40,XX mice studied, but abnormal (bicuspid or quadricuspid) in 15% of 39,XMO mice. Smooth muscle cell orientation in the ascending aorta was abnormal in all 39,XPO and 39,XMO mice examined, but smooth muscle actin was decreased in 39,XMO mice only. Aortic dilation was present with reduced penetrance in 39,XO mice. The 39,XO mouse demonstrates aortopathy and an X-linked parent-of-origin effect on aortic valve malformation, and the candidate gene FAM9B is polymorphically expressed in control and diseased human aortic valves. The 39,XO mouse model may be valuable for examining the mechanisms underlying the cardiovascular findings in TS, and suggest there are important genetic modifiers on the X chromosome that modulate risk for nonsyndromic BAV and aortopathy.<\/jats:p>","DOI":"10.3390\/jcdd2030190","type":"journal-article","created":{"date-parts":[[2015,7,13]],"date-time":"2015-07-13T03:49:22Z","timestamp":1436759362000},"page":"190-199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preliminary Evidence for Aortopathy and an X-Linked  Parent-of-Origin Effect on Aortic Valve Malformation in a Mouse Model of Turner Syndrome"],"prefix":"10.3390","volume":"2","author":[{"given":"Robert","family":"Hinton","sequence":"first","affiliation":[{"name":"The Heart Institute, Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Opoka","sequence":"additional","affiliation":[{"name":"The Heart Institute, Division of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obah","family":"Ojarikre","sequence":"additional","affiliation":[{"name":"Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics and Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Neuroscience and Mental Health Research Institute, Schools of Medicine and Psychology,  Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Davies","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics and Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Neuroscience and Mental Health Research Institute, Schools of Medicine and Psychology,  Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMra030360","article-title":"Turner\u2019s syndrome","volume":"351","author":"Sybert","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1016\/j.jacc.2008.02.035","article-title":"Aortic valve disease in Turner syndrome","volume":"51","author":"Sachdev","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1542\/peds.101.1.e11","article-title":"Cardiovascular malformations and complications in Turner syndrome","volume":"101","author":"Sybert","year":"1998","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1542\/peds.102.1.e12","article-title":"Further delineation of aortic dilation, dissection, and rupture in patients with Turner syndrome","volume":"102","author":"Lin","year":"1998","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nature03479","article-title":"X-inactivation profile reveals extensive variability in X-linked gene expression in females","volume":"434","author":"Carrel","year":"2005","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1136\/jmg.31.11.840","article-title":"Possible role of imprinting in the Turner phenotype","volume":"31","author":"Chu","year":"1994","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8567","DOI":"10.1523\/JNEUROSCI.5810-12.2013","article-title":"Genomic imprinting effects of the X chromosome on brain morphology","volume":"33","author":"Lepage","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1210\/jc.2006-0158","article-title":"Clinical significance of the parental origin of the X chromosome in turner syndrome","volume":"92","author":"Sagi","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/42706","article-title":"Evidence from Turner\u2019s syndrome of an imprinted X-linked locus affecting cognitive function","volume":"387","author":"Skuse","year":"1997","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/cen.12481","article-title":"X Chromosome Parental Origin and Aortic Stiffness in Turner Syndrome","volume":"81","author":"Bakalov","year":"2014","journal-title":"Clin. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1136\/hrt.75.5.434","article-title":"The pathogenesis of spontaneous arterial dissection","volume":"75","author":"Davies","year":"1996","journal-title":"Heart"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00439-007-0324-4","article-title":"The physical phenotype of girls and women with Turner syndrome is not X-imprinted","volume":"121","author":"Bondy","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1365-2265.2010.03782.x","article-title":"Influence of parental origin of the X chromosome on physical phenotypes and GH responsiveness of patients with Turner syndrome","volume":"73","author":"Ko","year":"2010","journal-title":"Clin. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/bies.20341","article-title":"X-linked imprinting: Effects on brain and behaviour","volume":"28","author":"Davies","year":"2006","journal-title":"Bioessays"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/37514","article-title":"Mosaicism in Turner\u2019s syndrome","volume":"390","author":"Henn","year":"1997","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/ng1577","article-title":"Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice","volume":"37","author":"Davies","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bbr.2007.02.013","article-title":"The 39,XO mouse as a model for the neurobiology of Turner syndrome and sex-biased neuropsychiatric disorders","volume":"179","author":"Lynn","year":"2007","journal-title":"Behav. Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"926975","DOI":"10.1155\/2012\/926975","article-title":"Bicuspid aortic valve and thoracic aortic aneurysm: Three patient populations, two disease phenotypes, and one shared genotype","volume":"2012","author":"Hinton","year":"2012","journal-title":"Cardiol. Res. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"H2480","DOI":"10.1152\/ajpheart.91431.2007","article-title":"Mouse heart valve structure and function: Echocardiographic and morphometric analyses from the fetus through the aged adult","volume":"294","author":"Hinton","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1161\/CIRCULATIONAHA.106.685487","article-title":"Aortic dilatation and dissection in Turner syndrome","volume":"116","author":"Matura","year":"2007","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1161\/CIRCULATIONAHA.111.088633","article-title":"Moderate aortic enlargement and bicuspid aortic valve are associated with aortic dissection in Turner syndrome: Report of the international turner syndrome aortic dissection registry","volume":"126","author":"Carlson","year":"2012","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1161\/01.RES.0000224114.65109.4e","article-title":"Extracellular matrix remodeling and organization in developing and diseased aortic valves","volume":"98","author":"Hinton","year":"2006","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.RES.88.1.37","article-title":"Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome","volume":"88","author":"Bunton","year":"2001","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1161\/CIRCIMAGING.113.000526","article-title":"Spectrum of aortic valve abnormalities associated with aortic dilation across age groups in Turner syndrome","volume":"6","author":"Olivieri","year":"2013","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/heart.83.1.81","article-title":"Clinical significance of the bicuspid aortic valve","volume":"83","author":"Ward","year":"2000","journal-title":"Heart"},{"key":"ref_26","first-page":"445","article-title":"Coarctation of the aorta in Turner syndrome: A pathologic study of fetuses with nuchal cystic hygromas, hydrops fetalis, and female genitalia","volume":"81","author":"Lacro","year":"1988","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3109\/14767058.2011.564688","article-title":"Outcome of fetuses with Turner syndrome: A 10-year congenital anomaly register based study","volume":"25","author":"Iyer","year":"2012","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.1111\/j.1749-6632.2010.05567.x","article-title":"Genomic imprinting on the X chromosome: Implications for brain and behavioral phenotypes","volume":"1204","author":"Davies","year":"2010","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1136\/jmedgenet-2013-101720","article-title":"Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome","volume":"50","author":"Bondy","year":"2013","journal-title":"J. Med. Genet."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/2\/3\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:49:00Z","timestamp":1760215740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/2\/3\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,10]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["jcdd2030190"],"URL":"https:\/\/doi.org\/10.3390\/jcdd2030190","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,10]]}}}