Effects of thyroxine exposure on the Twist 1 +/− phenotype: A test of gene–environment interaction modeling for craniosynostosis

Emily L. Durham, R. Nicole Howie, Laurel Black, Grace Bennfors, Trish E. Parsons, Mohammed Elsayed Elsalanty, Jack C Yu, Seth M. Weinberg, James J. Cray

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)803-813
Number of pages11
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume106
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Craniosynostoses
Thyroxine
Cranial Sutures
Phenotype
Thyroid Hormones
Gene Expression
Genetic Models
Sutures
Thyroid Gland
Cohort Studies
Parturition
Mutation
Therapeutics
Research

Keywords

  • cephalometrics
  • cranial suture
  • craniosynostosis
  • gene expression
  • thyroid hormone

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Developmental Biology

Cite this

Effects of thyroxine exposure on the Twist 1 +/− phenotype : A test of gene–environment interaction modeling for craniosynostosis. / Durham, Emily L.; Howie, R. Nicole; Black, Laurel; Bennfors, Grace; Parsons, Trish E.; Elsalanty, Mohammed Elsayed; Yu, Jack C; Weinberg, Seth M.; Cray, James J.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 106, No. 10, 01.10.2016, p. 803-813.

Research output: Contribution to journalArticle

Durham, Emily L. ; Howie, R. Nicole ; Black, Laurel ; Bennfors, Grace ; Parsons, Trish E. ; Elsalanty, Mohammed Elsayed ; Yu, Jack C ; Weinberg, Seth M. ; Cray, James J. / Effects of thyroxine exposure on the Twist 1 +/− phenotype : A test of gene–environment interaction modeling for craniosynostosis. In: Birth Defects Research Part A - Clinical and Molecular Teratology. 2016 ; Vol. 106, No. 10. pp. 803-813.
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