Mammalian Genome

, Volume 16, Issue 6, pp 424–431 | Cite as

Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader–Willi syndrome mouse models

  • Feng Ding
  • Yelena Prints
  • Madhu S. Dhar
  • Dabney K. Johnson
  • Carmen Garnacho–Montero
  • Robert D. Nicholls
  • Uta FranckeEmail author


Prader–Willi syndrome (PWS) is a neurobehavioral disorder caused by the lack of paternal expression of imprinted genes in the human chromosome region 15q11–13. Recent studies of rare human translocation patients narrowed the PWS critical genes to a 121-kb region containing PWCR1/HBII-85 and HBII-438 snoRNA genes. The existing mouse models of PWS that lack the expression of multiple genes, including Snrpn, Ube3a, and many intronic snoRNA genes, are characterized by 80%–100% neonatal lethality. To define the candidate region for PWS-like phenotypes in mice, we analyzed the expression of several genetic elements in mice carrying the large radiation-induced p 30PUb deletion that includes the p locus. Mice having inherited this deletion from either parent develop normally into adulthood. By Northern blot and RT-PCR assays of brain tissue, we found that Pwcr1/MBII-85 snoRNAs are expressed normally, while MBII-52 snoRNAs are not expressed when the deletion is paternally inherited. Mapping of the distal deletion breakpoint indicated that the p 30PUb deletion includes the entire MBII-52 snoRNA gene cluster and three previously unmapped EST sequences. The lack of expression of these elements in mice with a paternal p 30PUb deletion indicates that they are not critical for the neonatal lethality observed in PWS mouse models. In addition, we identified MBII-436, the mouse homolog of the HBII-436 snoRNA, confirmed its imprinting status, and mapped it outside of the p 30PUb deletion. Taking together all available data, we conclude that the lack of Pwcr1/MBII-85 snoRNA expression is the most likely cause for the neonatal lethality in PWS model mice.


snoRNA Gene Duplex Polymerase Chain Reaction Neonatal Lethality Paternal Expression Exist Mouse Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Art Beaudet, Baylor College of Medicine, for the SnrpnUbe3a deletion mouse strain, and the members of the Francke lab for generous help and discussion. This work was supported by NIH grant R01 HD 41623 (U.F.), by a Charles E. Culpeper Biomedical Pilot Initiative grant from the Rockefeller Brothers Fund (U.F), and by a grant from the Foundation for Prader–Willi Research (U.F.).


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Copyright information

© Springer Science+Business Media Inc. 2005

Authors and Affiliations

  • Feng Ding
    • 1
  • Yelena Prints
    • 1
  • Madhu S. Dhar
    • 2
  • Dabney K. Johnson
    • 3
  • Carmen Garnacho–Montero
    • 4
  • Robert D. Nicholls
    • 4
  • Uta Francke
    • 1
    • 5
    Email author
  1. 1.Department of GeneticsStanford UniversityStanfordUSA
  2. 2.Department of NutritionUniversity of TennesseeKnoxvilleUSA
  3. 3.Life Sciences DivisionOak Ridge National LaboratoryOak RidgeUSA
  4. 4.Center for Neurobiology and Behavior, Departments of Psychiatry and GeneticsUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Stanford University School of MedicineBeckman Center for Molecular and Genetic MedicineStanfordUSA

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