A mouse model for Prader-Willi syndrome imprinting-centre mutations.
Imprinting in the 15q11-q13 region involves an 'imprinting centre' (IC), mapping in part to the promoter and first exon of SNRPN. Deletion of this IC abolishes local paternally derived gene expression and results in Prader-Willi syndrome (PWS). We have created two deletion mutations in mice to understand PWS and the mechanism of this IC. Mice harbouring an intragenic deletion in Snrpn are phenotypically normal, suggesting that mutations of SNRPN are not sufficient to induce PWS. Mice with a larger deletion involving both Snrpn and the putative PWS-IC lack expression of the imprinted genes Zfp127 (mouse homologue of ZNF127), Ndn and Ipw, and manifest several phenotypes common to PWS infants. These data demonstrate that both the position of the IC and its role in the coordinate expression of genes is conserved between mouse and human, 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.
Yang
T
T
Department of Molecular Genetics and Microbiology, University of Florida Brain Institute, University of Florida College of Medicine, Gainesville 32610-0266, USA.
Adamson
T E
TE
Resnick
J L
JL
Leff
S
S
Wevrick
R
R
Francke
U
U
Jenkins
N A
NA
Copeland
N G
NG
Brannan
C I
CI
D000818:Animals; D001324:Autoantigens / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear; D017384:Sequence Deletion; D055517:snRNP Core Proteins
D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins