Genomic imprinting of Mash2 , a mouse gene required for trophoblast development

The mouse gene Mash2 encodes a transcription factor required for development of trophoblast progenitors. Mash2 − homozygous mutant embryos die at 10 days post–coitum from placental failure. Here we show that Mash2 is genomically imprinted. First, Mash2+/− embryos inheriting a wild–type allele from their father die at the same stage as −/− embryos, with a similar placental phenotype. Second, the Mash2 paternal allele is initially expressed by groups of trophoblast cells at 6.5 and 7.5 days post–coitum, but appears almost completely repressed by 8.5 days post–coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin–2 , insulin–like growth factor–2 and H19 .