A MOUSE MODEL FOR PRADER-WILLI-SYNDROME IMPRINTING-CENTER MUTATIONS

Imprinting in the 15q11-q13 region involves an 'imprinting centre' (IC ), mapping in part to the promoter and first exon of SNRPN. Deletion o f this IC abolishes local paternally derived gene expression and resul ts in Prader-Willi syndrome (PWS). We have created two deletion mutati ons in mice to understand PWS and the mechanism of this IC. Mice harbo uring an intragenic deletion in Snrpn are phenotypically normal, sugge sting that mutations of SNRPN are not sufficient to induce PWS. Mice w ith a larger deletion involving both Snrpn and the putative PWS-IC lac k expression of the imprinted genes Zfp127 (mouse homologue of ZNF127) Ndn and Ipw, and manifest several phenotypes common to PWS infants. T hese data demonstrate that both the position of the IC and its role in the coordinate expression of genes is conserved between mouse and hum an, and indicate that the mouse is a suitable model system in which to investigate the molecular mechanisms of imprinting in this region of the genome.