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Expression analysis of the ataxin–1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals

Nature Genetics volume 10, pages 94–98 (1995)Cite this article

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a GAG trinucleotide repeat which codes for glutamine in the protein ataxin–1. We have investigated the effect of this expansion on ataxin–1 by immunoblot analysis. The wild–type protein is detected in both normal and affected individuals; however, a mutant protein which varies in its migration properties according to the size of the GAG repeat is detected in cultured cells and tissues from SCA1 individuals. The protein has a nuclear localization in all normal and SCA1 brain regions examined but a cytoplasmic localization of ataxin–1 was also observed in cerebellar Purkinje cells. Our data show that in SCA1, the expanded alleles are faithfully translated into proteins of apparently normal stability and distribution.

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References

  1. Zoghbi, H.Y. The spinocerebellar degenerations. in Current Neurology (ed. Appel, S.H.) 87–110 (Mosby-Year Book, Inc., St. Louis, 1993).

    Google Scholar 

  2. Orr, H. et al. Expansion of an unstable trinucleotide (CAG) repeat in spinocerebellar ataxia type 1. Nature Genet. 4, 221–226 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. Banfi, S. et al. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nature Genet. 7, 513–519 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Willems, P.J. Dynamic mutations hit double figures. Nature Genet. 8, 213–215 (1994).

    Article  CAS  PubMed  Google Scholar 

  5. La Spada, A.R., Wilson, E.M., Lubahn, D.B., Harding, A.E. & Fischbeck, H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971–983 (1993).

    Article  Google Scholar 

  7. Koide, R. et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nature Genet. 6, 9–13 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Nagafuchi, S. et al. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nature Genet. 6, 14–18 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Burke, J.R. et al. The Haw River Syndrome: Dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nature Genet. 7, 521–524 (1994).

    Article  CAS  PubMed  Google Scholar 

  10. Kawaguchi, Y. et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genet. 8, 221–227 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Matilla, T., McCall, A., Subramony, S.H. & Zoghbi, H.Y. Molecular and clinical correlations in spinocerebellar ataxia type 3 and Machado-Joseph disease. Ann. Neurol. (in the press).

  12. Quigley, C.A. et al. Complete deletion of the androgen receptor gene: definition of the null phenotype of the androgen insensitivity syndrome and determination of carrier status. J. clin. endocrinol. Metab. 74, 927–933 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Trifiro, M. et al. The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene. Molec. cell. Endocrinol. 75, 37–47 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Gusella, J.F. et al. Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome. Nature 318, 75–78 (1985).

    Article  CAS  PubMed  Google Scholar 

  15. Wexler, N.S. et al. Homozygotes for Huntington's disease. Nature 326, 194–197 (1987).

    Article  CAS  PubMed  Google Scholar 

  16. Strong, T.V. et al. Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues. Nature Genet. 5, 259–265 (1993).

    Article  CAS  PubMed  Google Scholar 

  17. Li, S.-H. et al. Huntington's disease gene (IT15) is widely expressed in human and rat tissues. Neuron 11, 985–993 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Hoogeveen, A.T et al. Characterization and localization of the Huntington disease gene product. Hum. molec. Genet. 2, 2069–2073 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Ranum, L.P.W. et al. Molecular and clinical correlations in spinocerebellar ataxia type 1 (SCA1): evidence for familial effects on the age of onset. Am. J. hum. Genet. 55, 244–252 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Mhatre, A.M. et.al. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genet. 5, 184–188 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Courey, A.J. & Tijan, R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell 55, 887–898 (1988).

    Article  CAS  PubMed  Google Scholar 

  22. Pascal, E. & Tjian, R. Different activation domains of Sp1 govern formation of mutlimers and mediate transcriptional synergism. Genes Dev. 5, 1646–1656 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Perutz, M.F., Johnson, T., Suzuki, M. & Finch, J.T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases . Proc.natn. Acad. Sci. U.S.A. 91, 5355–5358 (1994).

    Article  CAS  Google Scholar 

  24. Green, H. Human genetic diseases due to codon reiteration: relationship to an evolutionary mechanism. Cell 74, 955–956 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Laemmli, E.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685 (1970).

    Article  CAS  PubMed  Google Scholar 

  26. Cattoretti, G. et alAntigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J. Pathol. 171, 83–98 (1993).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Antonio Servadio, Beena Koshy, Dawna Armstrong & Huda Y. Zoghbi

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Huda Y. Zoghbi

  3. Department of Pathology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Dawna Armstrong & Barbara Antalffy

  4. Department of Laboratory Medicine and Pathology, Department of Biochemistry, and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    Harry T. Orr

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  1. Antonio Servadio
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  2. Beena Koshy
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  4. Barbara Antalffy
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  5. Harry T. Orr
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  6. Huda Y. Zoghbi
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Servadio, A., Koshy, B., Armstrong, D. et al. Expression analysis of the ataxin–1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals. Nat Genet 10, 94–98 (1995). https://doi.org/10.1038/ng0595-94

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