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Craniofacial alterations may lead to complications in breathing, eating, and communication. Ts65Dn mice exhibit craniofacial alterations that model Down syndrome including a small mandible. We show that Ts65Dn embryos at 13.5 days gestation (E13.5) have a smaller mandibular precursor but a normal sized tongue as compared to euploid embryos, suggesting a relative instead of actual macroglossia originates during development. Neurological tissues were also altered in E13.5 trisomic embryos. Our array analysis found 155 differentially expressed non\u2010trisomic genes in the trisomic E13.5 mandible, including 20 genes containing a homeobox DNA binding domain. Additionally, <jats:italic>Sox9<\/jats:italic>, important in skeletal formation and cell proliferation, was upregulated in Ts65Dn mandible precursors. Our results suggest trisomy causes altered expression of non\u2010trisomic genes in development leading to structural changes associated with DS. Identification of genetic pathways disrupted by trisomy is an important step in proposing rational therapies at relevant time points to ameliorate craniofacial abnormalities in DS and other congenital disorders. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36006","type":"journal-article","created":{"date-parts":[[2013,7,10]],"date-time":"2013-07-10T16:19:08Z","timestamp":1373473148000},"page":"1866-1874","source":"Crossref","is-referenced-by-count":18,"title":["Non\u2010trisomic homeobox gene expression during craniofacial development in the Ts65Dn mouse model of Down syndrome"],"prefix":"10.1002","volume":"161","author":[{"given":"Cherie N.","family":"Billingsley","sequence":"first","affiliation":[{"name":"Department of Biology and Indiana University Center for Regenerative Biology and Medicine Indiana University\u2010Purdue University Indianapolis Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared 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