Moreau, Julie L. M and Kesteven, Scott and Martin, Ella M M A and Lau, Kin S and Yam, Michelle X and O'Reilly, Victoria C and del Monte-Nieto, Gonzalo and Baldini, Antonio and Feneley, Michael P and Moon, Anne M and Harvey, Richard P and Sparrow, Duncan B and Chapman, Gavin and Dunwoodie, Sally L (2019) Gene-environment interaction impacts on heart development and embryo survival. Development, 146 (4). pp. dev172957. ISSN 0950-1991 (Not OA)
Full text not available from this repository.Abstract
Congenital heart disease (CHD) is the most common type of birth defect. In recent years, research has focussed on identifying the genetic causes of CHD. However, only a minority of CHD cases can be attributed to single gene mutations. In addition, studies have identified different environmental stressors that promote CHD, but the additive effect of genetic susceptibility and environmental factors is poorly understood. In this context, we have investigated the effects of short-term gestational hypoxia on mouse embryos genetically predisposed to heart defects. Exposure of mouse embryos heterozygous for Tbx1 or Fgfr1/Fgfr2 to hypoxia in utero increased the incidence and severity of heart defects while Nkx2-5+/- embryos died within 2 days of hypoxic exposure. We identified the molecular consequences of the interaction between Nkx2-5 and short-term gestational hypoxia, which suggest that reduced Nkx2-5 expression and a prolonged hypoxia-inducible factor 1α response together precipitate embryo death. Our study provides insight into the causes of embryo loss and variable penetrance of monogenic CHD, and raises the possibility that cases of foetal death and CHD in humans could be caused by similar gene-environment interactions.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Mar 2019 04:35 |
| Last Modified: | 11 Mar 2019 04:35 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/812 |
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