Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.

Authors
Van de Pette, Mathew 
Creeth, Hugo DJ 
Lefebvre, Louis 
John, Rosalind M 

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Article
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Abstract

Beckwith-Wiedemann syndrome (BWS) is a complex imprinting disorder involving fetal overgrowth and placentomegaly, and is associated with a variety of genetic and epigenetic mutations affecting the 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 in 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.

Publication Date
2018-11-16
Online Publication Date
2018-11-16
Acceptance Date
2018-08-17
Keywords
Beckwith–Wiedemann syndrome, Fetal growth restriction, Mouse model, Placentomegaly, Animals, Basic Helix-Loop-Helix Transcription Factors, Beckwith-Wiedemann Syndrome, Biomarkers, Cell Lineage, Disease Models, Animal, Embryo Loss, Female, Fetal Growth Retardation, Fetus, Gene Expression Regulation, Developmental, Glycogen, Mice, Models, Genetic, Placenta, Pregnancy, Trophoblasts
Journal Title
Dis Model Mech
Journal ISSN
1754-8403
1754-8411
Volume Title
11
Publisher
The Company of Biologists
Sponsorship
Canadian Institutes of Health Research (MOP-451 119357) NSERC (RGPIN 386979-12) The Waterloo Foundation Ewan Maclean Fellowship