Gene-environment interaction impacts on heart development and embryo survival
| Autor: | Michelle Yam, Scott H. Kesteven, Ella M M A Martin, Sally L. Dunwoodie, Michael P. Feneley, Antonio Baldini, Duncan B. Sparrow, Anne M. Moon, Richard P. Harvey, Victoria C. O'Reilly, Gonzalo del Monte-Nieto, Kin S. Lau, Julie L. M. Moreau, Gavin Chapman |
|---|---|
| Přispěvatelé: | Moreau, Julie L M, Kesteven, Scott, Martin, Ella M M A, Lau, Kin S., Yam, Michelle X., O'Reilly, Victoria C., Del Monte-Nieto, Gonzalo, Baldini, Antonio, Feneley, Michael P., Moon, Anne M., Harvey, Richard P., Sparrow, Duncan B., Chapman, Gavin, Dunwoodie, Sally L. |
| Rok vydání: | 2018 |
| Předmět: |
TBX1
Heart Defects Congenital Male Heterozygote Time Factors Heart disease Physiology Apoptosis Mice Transgenic 030204 cardiovascular system & hematology Biology Embryogenesi 03 medical and health sciences Mice 0302 clinical medicine medicine Genetic predisposition Animals Genetic Predisposition to Disease Receptor Fibroblast Growth Factor Type 1 Hypoxia Molecular Biology 030304 developmental biology Congenital heart disease Cell Proliferation Homeodomain Proteins 0303 health sciences Heart development Embryogenesis Gene-environment Gestation Heart Embryo Hypoxia (medical) medicine.disease Embryo Mammalian Hypoxia-Inducible Factor 1 alpha Subunit Penetrance Mice Inbred C57BL Oxygen In utero embryonic structures Homeobox Protein Nkx-2.5 Female Gene-Environment Interaction medicine.symptom T-Box Domain Proteins Developmental Biology |
| Zdroj: | Development (Camb.) 146 (2019). doi:10.1242/dev.172957 info:cnr-pdr/source/autori:Moreau J.L.M.; Kesteven S.; Martin E.M.M.A.; Lau K.S.; Yam M.X.; O'reilly V.C.; Del Monte-Nieto G.; Baldini A.; Feneley M.P.; Moon A.M.; Harvey R.P.; Sparrow D.B.; Chapman G.; Dunwoodie S.L./titolo:Gene-environment interaction impacts on heart development and embryo survival/doi:10.1242%2Fdev.172957/rivista:Development (Camb.)/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume:146 |
| ISSN: | 1477-9129 |
| DOI: | 10.1242/dev.172957 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|