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Non‐trisomic homeobox gene expression during craniofacial development in the Ts65Dn mouse model of Down syndrome
Author(s) -
Billingsley Cherie N.,
Allen Jared R.,
Baumann Douglas D.,
Deitz Samantha L.,
Blazek Joshua D.,
Newbauer Abby,
Darrah Andrew,
Long Brad C.,
Young Brandon,
Clement Mark,
Doerge R.W.,
Roper Randall J.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36006
Subject(s) - homeobox , craniofacial , homeobox a1 , biology , genetics , gene , down syndrome , hnf1b , craniofacial abnormality , expression (computer science) , homeobox protein nkx 2.5 , gene expression , computer science , programming language
Trisomy 21 in humans causes cognitive impairment, craniofacial dysmorphology, and heart defects collectively referred to as Down syndrome. Yet, the pathophysiology of these phenotypes is not well understood. 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‐trisomic genes in the trisomic E13.5 mandible, including 20 genes containing a homeobox DNA binding domain. Additionally, Sox9 , important in skeletal formation and cell proliferation, was upregulated in Ts65Dn mandible precursors. Our results suggest trisomy causes altered expression of non‐trisomic 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. © 2013 Wiley Periodicals, Inc.