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Reduced transcriptional regulatory competence of the androgen receptor in X–linked spinal and bulbar muscular atrophy

Nature Genetics volume 5, pages 184–188 (1993)Cite this article

A Correction to this article was published on 01 February 1994

Abstract

Expansion of the long (CAG; glutamine)n repeat in the first exon of the X–linked human androgen receptor gene (hAR) causes spinal and bulbar muscular atrophy, frequently in association with mild androgen insensitivity. The relevant normal motor neurons are preferentially stimulated by androgen, however no motor neuron disorder occurs with any other known AR mutation, including those that cause complete androgen insensitivity. We have found that a polyglutamine (Gln) expanded AR transactivates an androgen–responsive reporter gene subnormally. Other groups have reported that a poly Gln–deleted AR transactivates normally. A parsimonious interpretation of all these facts is that poly Gln expansion causes the AR to lose a function that is necessary for full androgen sensitivity and to gain a function that is selectively motor neuronotoxic.

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Author notes

  1. Anand N. Mhatre

    Present address: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis - Jewish General Hospital, 3755 Cote St. Catherine, Montreal, Quebec, H3T 1E2, Canada

    Anand N. Mhatre, Mark A. Trifiro, Morris Kaufman, Parsa Kazemi-Esfarjani & Leonard Pinsky

  2. Centre for Research in Neuroscience, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada

    Morris Kaufman, Denise Figlewicz & Guy Rouleau

  3. Department of Biology, McGill University, Montreal, Quebec, H3A 1B1, Canada

    Anand N. Mhatre, Parsa Kazemi-Esfarjani & Leonard Pinsky

  4. Department of Medicine, McGill University, Montreal, Quebec, H3A 1B1, Canada

    Mark A. Trifiro & Leonard Pinsky

  5. Department of Pediatrics, McGill University, Montreal, Quebec, H3A 1B1, Canada

    Leonard Pinsky

  6. Department of Neuroscience, McGill University, Montreal, Quebec, H3A 1B1, Canada

    Denise Figlewicz & Guy Rouleau

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Mhatre, A., Trifiro, M., Kaufman, M. et al. Reduced transcriptional regulatory competence of the androgen receptor in X–linked spinal and bulbar muscular atrophy. Nat Genet 5, 184–188 (1993). https://doi.org/10.1038/ng1093-184

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