Effects of thyroxine exposure on the Twist 1 +/- phenotype: A test of gene-environment interaction modeling for craniosynostosis.
Birth Defects Res A Clin Mol Teratol
; 106(10): 803-813, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27435288
ABSTRACT
BACKGROUND:
Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 11800 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) 106803-813, 2016. © 2016 Wiley Periodicals, Inc.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Tiroxina
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Anormalidades Induzidas por Medicamentos
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Proteínas Nucleares
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Craniossinostoses
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Proteína 1 Relacionada a Twist
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Interação Gene-Ambiente
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article