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A mouse model for Prader-Willi syndrome imprinting-centre mutations

Nature Genetics volume 19, pages 25–31 (1998)Cite this article

Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology and the Center for Mammalian Genetics,

    Tao Yang, Todd E. Adamson, James L. Resnick & Camilynn I. Brannan

  2. the University of Florida Brain Institute, University of Florida College of Medicine, Gainesville, Florida, 32610-0266, USA

    Tao Yang, Todd E. Adamson, James L. Resnick & Camilynn I. Brannan

  3. Cell Genesys Inc., 342 Lakeside Dr., Foster City, California, 94404, USA

    Stuart Leff

  4. Department of Medical Genetics, 659 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2

    Rachel Wevrick

  5. Department of Genetics and Howard Hughes Medical Institute, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, California, 94305-5428, USA

    Uta Francke

  6. Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, West 7th Street at Fort Detrick, Building 539, Frederick, Maryland, 21702-1201, USA

    Nancy A. Jenkins & Neal G. Copeland

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  1. Tao Yang
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Correspondence to Camilynn I. Brannan.

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Yang, T., Adamson, T., Resnick, J. et al. A mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet 19, 25–31 (1998). https://doi.org/10.1038/ng0598-25

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