MRC Mammalian Genetics Unit
The distal region of mouse Chr 2 is known to be subject to genomic imprinting. Our best candidate for imprinting is Gnas as there is clinical and biochemical evidence suggesting that its human homologue is paternally imprinted. Here we show an extra large transcript of Gnas, Gnasxl, maps into the imprinting region in the mouse and is exclusively paternally expressed. Gnasxl determines a variant G protein a subunit associated with the trans-Golgi network. We have identified another imprinted transcript using a protocol modified from representational difference analysis. In this protocol we cloned HpaII fragments differentially methylated on the maternal and paternal copies of distal Chr 2. A cloned difference product showed paternal methylation with maternal-specific expression and matched a transcript, Nesp, which lies at the Gnas locus. Nesp encodes a secreted protein of neuroendocrine tissues. Nesp, Gnasxl and Gnas are all part of the same transcription unit as transcripts of Nesp and Gnasxl are alternatively spliced onto exon 2 of Gnas. This is a new type of imprinting cluster in which two oppositely imprinted genes share the same downstream exons.