The role of the imprinted gene Peg1 in mammalian development

The paternally expressed gene 1 (Peg1), also known as mesodermally expressed specific transcript (Mest), is one of approximately 60 genes so far discovered, the expression of which is dependent on the parental origin of each gene copy. Human Peg1 and its highly conserved mouse counterpart are expressed primarily from the paternal genome. Initial investigations into the distribution of Peg1 expression have concluded that its mRNA is found exclusively in tissues of mesodermal origin and that expression levels decline substantially after birth. A lack of Peg1 expression in mice has been associated with a modest growth retardation at late gestation and abnormal maternal behaviour. Aside from this however, very little is known about the biochemical function or biological role of Peg1 in mammalian development. The data presented here show that from E7.5 onwards, Peg1 expression was strong in tissues of mesodermal origin, but there was clear evidence of additional expression in ectodermal tissues at the anterior end of the embryo, deriving from the neural plate. Mice lacking Peg1 expression were 5 – 15% growth retarded in embryo, placenta and kidney from embryonic day 14 onwards. They also exhibited specific irregularities in organogenesis, consisting of a 22% reduction in the total volume of maternal blood spaces in the labyrinthine placenta, and a 26% reduction in glomerular volume fraction in the kidney, attributed to fewer glomeruli in the mutant mouse. Significantly, Peg1 expression was absent in the trophoblast tissue that forms the maternal spaces in the labyrinthine placenta, being confined instead to the adjacent endothelial layer surrounding the fetal blood villi. In the kidney, Pe1l expression was strong in undifferentiated metanephric mesenchyme and also in glomeruli. Expression of human Peg1 in vitro caused substantial morphological change and cell death in one human fibroblast and two epithelial cell lines. Cell death induced by exogenous expression of Peg1 exhibited features common to both necrotic and apoptotic pathways.EThOS - Electronic Theses Online ServiceGBUnited Kingdo