{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:25:13Z","timestamp":1783488313322,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201907720056"],"award-info":[{"award-number":["201907720056"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT\/NCoR (silencing mediator retinoid and thyroid hormone receptors\/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C\/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+\/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C\/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.<\/jats:p>","DOI":"10.1093\/hmg\/ddac086","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:51:20Z","timestamp":1649854280000},"page":"2951-2963","source":"Crossref","is-referenced-by-count":10,"title":["An animal model for Pierpont syndrome: a mouse bearing the <i>Tbl1xr1<\/i>\n                  <i>Y446C\/Y446C<\/i> mutation"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0122-077X","authenticated-orcid":false,"given":"Yalan","family":"Hu","sequence":"first","affiliation":[{"name":"Endocrine Laboratory , Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lauffer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Stewart","sequence":"additional","affiliation":[{"name":"The Mary Lyon Centre , MRC Harwell, Harwell Campus, Oxfordshire OX11 0RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Codner","sequence":"additional","affiliation":[{"name":"The Mary Lyon Centre , MRC Harwell, Harwell Campus, Oxfordshire OX11 0RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Mayerl","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen 45122, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Heuer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen 45122, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Ng","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology , National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Forrest","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology , National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"van Trotsenburg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Emma Children\u2019s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Jongejan","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory , Department of Epidemiology and Data Science, Amsterdam Public Health, Methodology Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Fliers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Boelen","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory , Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"2022090105183001100_ref1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/(SICI)1096-8628(19980106)75:1<18::AID-AJMG5>3.0.CO;2-M","article-title":"Plantar lipomatosis, unusual facial phenotype and developmental delay: a new MCA\/MR syndrome","volume":"75","author":"Pierpont","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"2022090105183001100_ref2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/ajmg.a.30863","article-title":"Plantar lipomatosis, unusual facies, and developmental delay: confirmation of Pierpont syndrome","volume":"137","author":"Oudesluijs","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"2022090105183001100_ref3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3171\/2012.10.PEDS12219","article-title":"Choroid plexus papilloma and Pierpont syndrome","volume":"11","author":"Vadivelu","year":"2013","journal-title":"J. Neurosurg. Pediatr."},{"key":"2022090105183001100_ref4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1136\/jmedgenet-2015-103233","article-title":"A specific mutation in TBL1XR1 causes Pierpont syndrome","volume":"53","author":"Heinen","year":"2016","journal-title":"J. Med. Genet."},{"key":"2022090105183001100_ref5","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10930-018-9785-7","article-title":"WD40 repeat proteins: signalling scaffold with diverse functions","volume":"37","author":"Jain","year":"2018","journal-title":"Protein J."},{"key":"2022090105183001100_ref6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.tibs.2010.04.003","article-title":"WD40 proteins propel cellular networks","volume":"35","author":"Stirnimann","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"2022090105183001100_ref7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrendo.2013.58","article-title":"Making sense with thyroid hormone\u2014the role of T3 in auditory development","volume":"9","author":"Ng","year":"2013","journal-title":"Nat. Rev. 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