Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.
Disease models & mechanisms
Company of Biologists
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Tunster, S., Van De Pette, M., Creeth, H. D., Lefebvre, L., & John, R. M. (2018). Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.. Disease models & mechanisms, 11 (11)https://doi.org/10.1242/dmm.035832
Beckwith-Wiedemann syndrome (BWS) is a complex imprinting disorder involving fetal overgrowth and placentomegaly and associated with a variety of genetic and epigenetic mutations affecting expression of imprinted genes on human chromosome 11p15.5. Most BWS cases are linked to loss of methylation at the Imprint Control Region 2 (ICR2) within this domain, which in mice regulates the silencing of several maternally expressed imprinted genes. Modelling this disorder in mice is confounded by the unique embryonic requirement for Ascl2 which is imprinted in mice but not humans. To overcome this issue, we generated a novel model combining a truncation of distal chromosome 7 allele (DelTel7) with transgenic rescue of Ascl2 expression. This novel model recapitulated placentomegaly associated with BWS but did not lead to fetal overgrowth.
Trophoblasts, Fetus, Placenta, Animals, Mice, Embryo Loss, Fetal Growth Retardation, Beckwith-Wiedemann Syndrome, Disease Models, Animal, Glycogen, Gene Expression Regulation, Developmental, Cell Lineage, Pregnancy, Models, Genetic, Female, Basic Helix-Loop-Helix Transcription Factors, Biomarkers
Canadian Institutes of Health Research (MOP-451 119357) NSERC (RGPIN 386979-12) The Waterloo Foundation Ewan Maclean Fellowship
External DOI: https://doi.org/10.1242/dmm.035832
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284973
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/