{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T02:36:42Z","timestamp":1787539002911,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014371","name":"LuMind Research Down Syndrome Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014371","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Down syndrome (DS) is caused by an extra copy of human chromosome 21 (HSA21) and is associated with significant craniofacial anomalies among other systemic traits. While animal models have been pivotal in advancing DS research, most of the mouse models replicate only a portion of the human genetic condition. The recently developed transchromosomic rodent models of DS, TcMAC21 mice, and TcHSA21rat carry nearly complete copies of HSA21q and all of HSA21, respectively. While both TcMAC21 and TcHSA21rat express DS\u2010like craniofacial malformations, no comprehensive interspecies comparisons have been conducted between the two. Here, we quantitatively compare the craniofacial skeleton of TcMAC21, TcHSA21rat, and their respective unaffected littermates using high\u2010resolution micro\u2010computed tomography images, landmark\u2010based geometric morphometrics, and advanced multivariate statistics to assess overall craniofacial shape and integration patterns between the neurocranial and facial components. Both models reflect the craniofacial morphology of DS, exhibiting increased neurocranial globularity (supero\u2010inferiorly) and overall facial retraction (anteroposteriorly). However, the rat model expresses a more prominent brachycephalic phenotype compared with its murine counterpart. The integration between the cranial components was found to be evolutionarily conserved across species; however, the trisomic animals maintained their distinct DS\u2010specific configuration compared with their euploid littermates. Our findings establish a methodological framework for cross\u2010species comparisons in DS animal models and provide important insights into characteristic manifestations of trisomy 21 and evolutionarily conserved aspects of the mammalian craniofacial skeleton.<\/jats:p>","DOI":"10.1111\/joa.70066","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T04:31:31Z","timestamp":1763008291000},"page":"168-176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Craniofacial morphology of\n                    <scp>TcMAC21<\/scp>\n                    and\n                    <scp>TcHSA21rat<\/scp>\n                    models of Down syndrome: An interspecific comparison"],"prefix":"10.1111","volume":"249","author":[{"given":"Nandini","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Anthropology California State University  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger H.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology and Therapeutics and Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan T.","family":"Richtsmeier","sequence":"additional","affiliation":[{"name":"Department of Anthropology Pennsylvania State University  University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0143-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3458"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20833"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300325"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0254"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-016-9661-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icn076"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.029728"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1161147"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56223"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.12.015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ecolsys.37.091305.110054"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427\u2010016\u20100539\u20102"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/10635150590947258"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107580.2008.00900.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.815739"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20710"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026425"},{"key":"e_1_2_8_20_1","first-page":"4856","article-title":"Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with down syndrome","volume":"25","author":"McElyea S.D.","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11692\u2010012\u20109178\u20103"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.09.017"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00473.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114535"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201077"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(200002)217:2<137::AID-DVDY1>3.0.CO;2-N"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10175"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/106351500750049806"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2307\/2992207"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2007.00701.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhevol.2011.11.006"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.498"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.14012"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.anthro.34.081804.120613"},{"key":"e_1_2_8_35_1","unstructured":"Starbuck J.M. Harrington E. Kula K.S. Ghoneima A.A.&Roper R.J.(2014)3D Assessment of Nasopharyngeal and Craniofacial Phenotypes in Ts65Dn Down Syndrome Mice Treated with a Dyrk1a Inhibitor."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.119888"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2003.12.007"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76984-5"}],"container-title":["Journal of Anatomy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joa.70066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/joa.70066","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joa.70066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T03:23:16Z","timestamp":1780111396000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joa.70066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/joa.70066"],"URL":"https:\/\/doi.org\/10.1111\/joa.70066","archive":["Portico"],"relation":{},"ISSN":["0021-8782","1469-7580"],"issn-type":[{"value":"0021-8782","type":"print"},{"value":"1469-7580","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"2025-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}