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A candidate mouse model for Prader–Willi syndrome which shows an absence of Snrpn expression

Nature Genetics volume 2, pages 270–274 (1992)Cite this article

Abstract

The best examples of imprinting in humans are provided by the Angelman and Prader–Willi syndromes (AS and PWS) which are associated with maternal and paternal 15q11–13 deletions, respectively, and also with paternal and maternal disomy 15. The region of the deletions has homology with a central part of mouse chromosome 7, incompletely tested for imprinting effects. Here, we report that maternal duplication for this region causes a murine imprinting effect which may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with AS. Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely–linked Gabrb–3 locus is not subject to imprinting. Finally, an additional new imprinting effect is described.

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References

  1. Williams, C.A. et al. Maternal origin of 15q11-13 deletions in Angelman syndrome suggests a role for genomic imprinting. Am. J. med. Genet. 35, 350–353 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Nicholls, R.D., Knoll, J.H.M., Butler, M.G., Karam, S. & Lalande, M. Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature 342, 281–285 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pembrey, M. et al. The association of Angelman's syndrome with deletions within 15q11-13. J. med. Genet. 26, 73–77 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hamabe, J. et al. DNA deletion and its parental origin in Angelman syndrome patients. Am. J. med. Genet. 41, 64–68 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Knoll, J.H.M. et al. Angelman and Prader-Will syndromes have a common chromosome 15 deletion but differ in parental origin of the deletion. Am. J. med. Genet. 32, 285–290 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. Knoll, J.H.M. et al. Chromosome 15 unipafental disomy is not frequent in Angelman syndrome. Am. J. med. Genet. 48, 16–21 (1991).

    CAS  Google Scholar 

  7. Wagstaff, J. et al. Maternal but not paternal transmission of 15q11-13 linked non deletion Angelman syndrome leads to phenotypic expression. Nature Genet. 1, 291–294 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Butler, M.G. & Palmer, C.G. Parental origin of chromosome 15 deletion in Prader-Willi syndrome. Lancet 1, 1285–86 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mascari, M.J. et al. The frequency of uniparental disomy in Prader-Willi syndrome. New Eng. J. Med. 326, 1599–1607 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Özçelik, T. et al. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genet. (this issue).

  11. Nicholls, R.D., Gottlieb, W., Avidano, K., Williams, C.A. & Driscoll, D. Mouse chromosome mapping of clones from PWS/AS genetic region. Mouse Genome 89, 254 (1991).

    Google Scholar 

  12. Chaillet, R.J., Knoll, J.H.M., Horsthemke, B. & Lalande, M. The syntenic relationship between the critical deletion region for the Prader-Willi/Angelman Syndromes and proximal mouse chromosome 7. Genomics 11, 773–776 (1991).

    Article  CAS  PubMed  Google Scholar 

  13. Wagstaff, J., Chaillet, J.R. & Lalande, M. The GABAA receptor _3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7. Genomics 11, 1071–1078 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Cattanach, B.M. Chromosome imprinting and its significance for mammalian development. Genome Analysis 2, 41–71 (1991).

    Google Scholar 

  15. Searle, A.G. & Beechey, C.V. Genome imprinting phenomena on mouse chromosome 7. Genet. Res. 56, 237–244 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse Insulin-like growth factor II gene. Cell 64, 849–859 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Ferguson-Smith, A.C., Cattanach, B.M., Barton, S.C., Beechey, C.V. & Surani, M.A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351, 667–670 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Bartolomei, M.S., Zemel, S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Zemel, S., Bartolomei, M.S. & Tilghman, S.M. Physical linkage of two mammalian imprinted genes, H19 and Insulin-like growth factor 2. Nature Genetics 2, 61–65 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Williams, C.A., Gray, B.A., Hendrickson, J.E., Stone, J.W. & Cantu, E.S. Incidence of 15q deletions in the Angelman syndrome: A survey of 12 affected persons. Am. J. med. Genet. 32, 339–345 (1989).

    Article  CAS  PubMed  Google Scholar 

  21. Magenis, R. E. et al. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin and clinical consequence. Am. J. med. Genet. 35, 333–349 (1990).

    Article  CAS  PubMed  Google Scholar 

  22. Cassidy, S.B. & Ledbetter, D.H. Prader-Willi syndrome. Neurology Clinics 7, 37–54 (1989).

    Article  CAS  Google Scholar 

  23. Butler, M.G. Prader-Willi syndrome: current understanding of cause and diagnosis. Am. J. med. Genet. 35, 319–332 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Searle, A.G. & Beechey, C.V. Non-complementation phenomena and their bearing on non-disjunctional effects. In: Aneuploidy (Ed V.L. Dellaraco, P.E. Voytek, & A. Hollaender 363–376) (Plenum Press Inc. 1985).

    Chapter  Google Scholar 

  25. Cattanach, B.M. A chemically-induced variegated-type position effect in the mouse. Z. Vererbungsl 92, 165–182 (1961).

    CAS  PubMed  Google Scholar 

  26. Leff, S.E. et al. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with Prader-Willi syndrome region of humans. Nature Genet. (this issue).

  27. Forejt, J. & Gregorová, S. Genetic analysis of genomic imprinting: An imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus. Cell 70, 443–450 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Barlow, D.P., Stöger, R., Herrmann, B.G., Saito, K. & Schweifer, N. The mouse insulin-like growth factor type 2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84–87 (1991).

    Article  CAS  PubMed  Google Scholar 

  29. Bartolomei, M.S. & Tilghman, S.M. Parental imprinting of mouse chromosome 7. Semin. devel. Biol. 3, 107–117 (1992).

    Google Scholar 

  30. Moore, T. & Haig, D. Genomic imprinting in mammalian development: a parental tug of war. Trends Genet. 7, 45–49 (1991).

    Article  CAS  PubMed  Google Scholar 

  31. Evans, E.P. T(7;15)9H, correction of breakpoint. Mouse Genome 90, 210 (1990).

    Google Scholar 

  32. Evans, E.P. T(7;18)50H. Refinement of breakpoints. Mouse Genome 89, 551 (1991).

    Google Scholar 

  33. Chomczynski, P. & Sacchi, N. Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159 (1987).

    Article  CAS  PubMed  Google Scholar 

  34. Maniatis, T., Fritsch, E.F. & Sambrook, J. (eds) Molecular cloning: A laboratory manual, Cold Spring Harbor, NY (1982).

    Google Scholar 

  35. Minty, A.J., Alonso, S., Caravatti, M. & Buckingham, M.E. A fetal skeletal muscle actin mRNA in the mouse and it's identity with cardiac actin mRNA. Cell 30, 185–192 (1982).

    Article  CAS  PubMed  Google Scholar 

  36. Church, G.M. & Gilbert, W. Genomic Sequencing Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  CAS  Google Scholar 

  37. Wagstaff, J. et al. Localisation of the gene encoding the GABAA receptor _3 subunit to the AS/PWS region of human chromosome 15. Am. J. hum. Genet. 49, 330–337 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Mitchell, M.J., Woods, D.R., Tucker, P.K., Opp, J.S. & Bishop, C.E. Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme E1. Nature 354, 483–486 (1991).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Genetics, MRC Radiobiology Unit, Chilton, Didcot, Oxon, Ox11 ORD, UK

    Bruce M. Cattanach, Jacqueline A. Barr, Edward P. Evans, Michael Burtenshaw, Colin V. Beechey & Janet Jones

  2. Department of Pharmacology, Stanford University School of Medicine, Stanford, California, 94305, USA

    Stuart E. Leff

  3. Mammalian Genetics Laboratory, ABL-Basic Research Program NCI Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    Camilynn I. Brannan, Neal G. Copeland & Nancy A. Jenkins

Authors
  1. Bruce M. Cattanach
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  2. Jacqueline A. Barr
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  3. Edward P. Evans
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  4. Michael Burtenshaw
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  6. Stuart E. Leff
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Cattanach, B., Barr, J., Evans, E. et al. A candidate mouse model for Prader–Willi syndrome which shows an absence of Snrpn expression. Nat Genet 2, 270–274 (1992). https://doi.org/10.1038/ng1292-270

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