Conflict of interest: none.
Non-trisomic homeobox gene expression during craniofacial development in the Ts65Dn mouse model of Down syndrome
Article first published online: 10 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 8, pages 1866–1874, August 2013
How to Cite
2013. Non-trisomic homeobox gene expression during craniofacial development in the Ts65Dn mouse model of Down syndrome. Am J Med Genet Part A. 161A:1866–1874., , , , , , , , , , , .
- Issue published online: 24 JUL 2013
- Article first published online: 10 JUL 2013
- Manuscript Accepted: 8 APR 2013
- Manuscript Received: 18 OCT 2012
- Research Support Funds
- Undergraduate Research Opportunity
- Beaty-C/Tech Fund–Blue River Community Foundation
- National Science Foundation GK-12 Urban Educators Program at IUPUI NSF. Grant Number: DGE0742475
- National Institutes of Health. Grant Number: DE021034
- trisomy 21;
- experimental animal models;
- developmental delay disorders;
- genotype–phenotype correlation
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.