DNA methylation constitutes an epigenetic modification of DNA that is initiated during gametogenesis and is essential for normal development. Methylation is postulated to be the molecular mark underlying genomic imprinting whereby genes are differentially expressed according to parental origin. The loss of the oocyte-derived DNMT1o maintenance methyltransferase affects the methylation imprints during preimplantation development, producing epigenetic mosaic embryos. Here we show that embryos that develop in the absence of DNMT1o demonstrate profound phenotypic variation in both fetal and extraembryonic tissues, as well as severe pregnancy loss by midgestation. Morphological assessment was complemented with methylation analysis of fetal and extraembryonic tissues at the differentially methylated domain (DMD) of the imprinted gene Snrpn. The general conclusion from this study is that extragenetic programming in the embryo greatly influences pregnancy outcome and phenotype in mouse embryos. The relevance of this work to human imprinting disorders and cloning technologies is discussed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82440 |
| Date | January 2004 |
| Creators | Toppings, Marc |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198706, proquestno: AAIMR12555, Theses scanned by UMI/ProQuest. |
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