Placental defects revealed by modelling PWS in mice

Abstract The neurodevelopmental disorder Prader-Willi syndrome (PWS) is caused by loss of paternally-derived gene expression from the imprinted interval on chromosome 15q11-q13. Recently, it has been suggested that the abnormal feeding-related behaviours characteristic of PWS may, in part, be developmentally programmed in utero via abnormal placental function. Here we report that several PWS-genes are expressed in mouse placenta with three PWS-transcripts Magel2, Necdin and the lncRNA Sngh14, co-localising to the Kdr-positive fetal endothelial cells of the labyrinth zone central to nutrient transport. In a novel PWS deletion mouse model (Large+/-) we find markedly reduced expression of PWS genes in the placenta and an associated ∼25% reduction in Kdr-positive fetal endothelial cells. Although this did not directly translate into a significant reduction in fetal growth late in gestation, these data suggest that placental function and nutrient transfer from mother to fetus could be compromised in PWS contributing to later post-natal phenotypes. Summary statement Reduced expression of PWS-associated genes in the mouse placenta results in a 25% loss of the fetal endothelial cells that play a central role in nutrient and gas exchange. Competing Interest Statement The authors have declared no competing interest. Footnotes The manuscript now contains additional data examining the expression of PWS gene Magel2 using RNAscope. There are also further descriptive analyses of proportions of cells co-expressing PWS genes and Kdr, and an additional Supporting Table (Table S7). To reflect these additional data, another author has been added. The text (including the title) has also been changed to soften the conclusion relating to functional changes in the PWS placenta. Additionally more details have been included relating to the PWS model used and the selection of the PWS genes analysed.