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Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice

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A Correction to this article was published on 01 June 1995

Abstract

The expansion of trinucleotide repeat sequences underlies a number of hereditary neurological disorders. To study the stability of a trinucleotide repeat and to develop an animal model of one of these disorders, spinal and bulbar muscular atrophy (SBMA), we have generated transgenic mice carrying either the normal or expanded repeat human androgen receptor (AR) gene. Unlike the disease allele in humans, the AR cDNA containing the expanded repeat in transgenic mice showed no change in repeat length with transmission. Expression of the SBMA AR was found in transgenic mice, but at a lower level than normal endogenous expression. The lack of a physiological pattern of expression may explain why no phenotypic effects of the transgene were observed.

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References

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

    Article  CAS  Google Scholar 

  2. Macdonald, M.E. et al. 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 

  3. Orr, H.T. et al. Expansion of an unstable trinucleotide CAG repeat In spinocerebeilar ataxia type-1. Nature Genet. 4, 221–226 (1993).

    Article  CAS  Google Scholar 

  4. Koide, R.T. et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallldoluysian atrophy (DRPLA). Nature Genetics 6, 9–13 (1994).

    Article  CAS  Google Scholar 

  5. Sobue, G. et al. X-linked recessive bulbospinal nueronopathy. A clinicopathological study. Brain 112, 209–232 (1989).

    Article  Google Scholar 

  6. La Spada, A.R. et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat In X-linked spinal and bulbar muscular atrophy. Nature Genet. 2, 301–304 (1992).

    Article  CAS  Google Scholar 

  7. Biancalana, V. et al. Moderate Instability of the trinucleotide repeat in spino-bulbar muscular atrophy. Hum. molec. Genet 1, 255–258 (1992).

    Article  CAS  Google Scholar 

  8. Igarashi, S. et al. Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. Neurology 42, 2300–2302 (1992).

    Article  CAS  Google Scholar 

  9. Doyu, M. et al. Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. Ann. Neurol. 32, 707–710 (1992).

    Article  CAS  Google Scholar 

  10. Arnheiter, H., Skuntz, S., Noteborn, M., Chang, S. & Meier, E.S. Transgenic mice with intra cellular immunity to Influenza virus. Cell 62, 51–61 (1990).

    Article  CAS  Google Scholar 

  11. Forss-Petter, S. et al. Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control. Neuron 5, 187–197 (1990).

    Article  CAS  Google Scholar 

  12. He, W.W. et al. Molecular cloning of androgen receptors from divergent species with a polymerase chain reaction technique: complete cDNA sequence of the mouse androgen receptor and isolation of androgen receptor cDNA probes from dog, guinea pig and clawed frog. Biochem. Biophys. Res. Commun. 171, 697–704 (1990).

    Article  CAS  Google Scholar 

  13. Husmann, D.A., Wilson, C., McPhaul, M.J., Tilley, W.D. & Wilson, J.D. Antipeptlde antibodies to two distinct regions of the androgen receptor localize the receptor protein to the nuclei of target cells in the rat and human prostate. Endocrinology 126, 2359–2368 (1990).

    Article  CAS  Google Scholar 

  14. He, W.W., Kumar, M.V. & Tindall, D.J. Aframe-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucl. Acids Res. 19, 2373–2378 (1991).

    Article  CAS  Google Scholar 

  15. Fishel, R. et al. The human mutator gene homolog msh2 and its association with hereditary nonpolyposis colon-cancer. Cell 75, 1027–1038 (1993).

    Article  CAS  Google Scholar 

  16. Strand, M., Prolla, T.A., Liskay, R.M. & Petes, T.D. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DMA mismatch repair. Nature 365, 274–276 (1993).

    Article  CAS  Google Scholar 

  17. Richards, R.I., Holman, K., Yu, S. & Sutherland, G.R. Fragile X syndrome unstable element, p(CGG)n, and other simple tandem repeat sequences are binding sites for specific nuclear proteins. Hum. molec. Genet. 2, 1429–1435 (1993).

    Article  CAS  Google Scholar 

  18. Mhatre, A.N. et al. Reduced transcriptional regulatory competence of the androgen receptor in x-llnked spinal and bulbar muscular-atrophy. Nature Genet. 5, 184–188 (1993).

    Article  CAS  Google Scholar 

  19. Sar, M. & Stumpf, W.E. Androgen concentration in motor neurons of cranial nerves and spinal cord. Science 197, 77–79 (1977).

    Article  CAS  Google Scholar 

  20. Forger, N.G., Hodges, L.L., Roberts, S.L. & Breedlove, S.M. Regulation of motoneuron death in the spinal nucleus of the bulbocavemosus. J. Neurobiol. 23, 1192–1203 (1992).

    Article  CAS  Google Scholar 

  21. Araki, I., Harada, Y. & Kuno, M. Target-dependent hormonal control of neuron size in the rat spinal nucleus of the bulbocavernosus. J. Neurosci. 11, 3025–3033 (1991).

    Article  CAS  Google Scholar 

  22. Fishman, R.B. & Breedlove, S.M. Local perineal implants of antiandrogen block masculinlzation of the spinal nucleus of the bulbocavemosus. Devel. Brain Res. 70, 283–286 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Simental, J.A., Star, M., Lane, M.V., French, F.S. & Wilson, E.M. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J. biol. Chem. 266, 510–518 (1991).

    CAS  Google Scholar 

  25. Palmiter, R.D. & Brinster, R.L. Germ-line transformation of mice. A. Rev. Genet. 20, 465–499 (1986).

    Article  CAS  Google Scholar 

  26. Sanger, F., Niklen, S. & Coulson, R. DNA sequencing with chain-terminating inhibitors. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Neurology, Children's Hospital of Philadelphia & Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Peter M. Bingham

  2. Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Marion O. Scott, Suping Wang, James Y. Garbern, Diane E. Merry & Kenneth H. Fischbeck

  3. Department of Internal Medicine, University of Texas Southwest Medical Center at Dallas, Texas, 75235, USA

    Michael J. McPhaul

  4. Laboratories for Reproductive Biology, Department of Biochemistry, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Elizabeth M. Wilson

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  1. Peter M. Bingham
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  2. Marion O. Scott
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  3. Suping Wang
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  4. Michael J. McPhaul
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  5. Elizabeth M. Wilson
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  6. James Y. Garbern
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  7. Diane E. Merry
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  8. Kenneth H. Fischbeck
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Bingham, P., Scott, M., Wang, S. et al. Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat Genet 9, 191–196 (1995). https://doi.org/10.1038/ng0295-191

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  • DOI: https://doi.org/10.1038/ng0295-191

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