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Effects of thyroxine exposure on the Twist 1 +/− phenotype: A test of gene-environment interaction modeling for craniosynostosis
Background Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human patients. Case, cohort, and surveillance studies have identified excess thyroid...
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Published in: | Birth defects research. A Clinical and molecular teratology 2016-10, Vol.106 (10), p.803-813 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background
Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human patients. Case, cohort, and surveillance studies have identified excess thyroid hormone as an agent that can either cause or exacerbate human cases of craniosynostosis.
Methods
Here we investigate the influence of in utero and in vitro exogenous thyroid hormone exposure on a murine model of craniosynostosis, Twist 1 +/−.
Results
By 15 days post‐natal, there was evidence of coronal suture fusion in the Twist 1 +/− model, regardless of exposure. With the exception of craniofacial width, there were no significant effects of exposure; however, the Twist 1 +/− phenotype was significantly different from the wild‐type control. Twist 1 +/− cranial suture cells did not respond to thyroxine treatment as measured by proliferation, osteogenic differentiation, and gene expression of osteogenic markers. However, treatment of these cells did result in modulation of thyroid associated gene expression.
Conclusion
Our findings suggest the phenotypic effects of the genetic mutation largely outweighed the effects of thyroxine exposure in the Twist 1 +/− model. These results highlight difficultly in experimentally modeling gene–environment interactions for craniosynostotic phenotypes. Birth Defects Research (Part A) 106:803–813, 2016. © 2016 Wiley Periodicals, Inc. |
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ISSN: | 1542-0752 1542-0760 |
DOI: | 10.1002/bdra.23543 |