Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Structure and Tissue Distribution of a Trinucleotide-Repeat-containing Gene (cag-3) Expressed Specifically in the Mouse Brain

  • Ji, Jin Woo (Department of Biology, Dongguk University) ;
  • Yang, Hye Lim (Department of Biology, Dongguk University) ;
  • Kim, Sun Jung (Department of Biology, Dongguk University)
  • Received : 2005.06.03
  • Accepted : 2005.08.22
  • Published : 2005.12.31
⟨ Previous Next ⟩

Abstract

Using in silico approaches and RACE we cloned a full length trinucleotide (CAG) repeat-containing cDNA (cag-3). The cDNA is 2478 bp long and the deduced polypeptide consists of 140 amino acids of which 73 are glutamines. The genomic sequence spans approximately 79 kb on mouse chromosome 7 and the gene is composed of four exons. Standard and real-time PCR analyses of several mouse tissues showed that the gene is exclusively expressed in the brain and is not detected in embryonic stages. Within the brain, it is expressed throughout the forebrain region with predominant expression in the hypothalamus and olfactory bulb and very low levels in the mid- and hindbrain.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Bhide, P. G., Day, M., Sapp, E., Schwarz, C., Sheth, A., et al. (1996) Expression of normal and mutant huntingtin in the developing brain. J. Neurosci. 16, 5523-5535
  2. Brown, L. Y. and Brown, S. A. (2004) Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet. 20, 51-58 https://doi.org/10.1016/j.tig.2003.11.002
  3. Burke, J. R., Wingfield, M. S., Lewis, K. E., Roses, A. D., Lee, J. E., et al. (1994) The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nat. Genet. 7, 521-524 https://doi.org/10.1038/ng0894-521
  4. Chevalier-Larsen, E. S., O'Brien, C. J., Wang, H., Jenkins, S. C., Holder, L., et al. (2004) Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy. J. Neurosci. 24, 4778-4786 https://doi.org/10.1523/JNEUROSCI.0808-04.2004
  5. Faux, N. G., Bottomley, S. P., Lesk, A. M., Irving, J. A., Morrison, J. R., et al. (2005) Functional insights from the distribution and role of homopeptide repeat-containing proteins. Genome Res. 15, 537-551 https://doi.org/10.1101/gr.3096505
  6. Freiman, R. N. and Tjian, R. (2002) Neurodegeneration. A glutamine-rich trail leads to transcription factors. Science 296, 2149-2150 https://doi.org/10.1126/science.1073845
  7. Gaspar, C., Jannatipour, M., Dion, P., Laganiere, J., Sequeiros, J., et al. (2000) CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation. Hum. Mol. Genet. 9, 1957-1966 https://doi.org/10.1093/hmg/9.13.1957
  8. Gomes-Pereira, M., Fortune, M. T., Ingram, L., McAbney, J. P., and Monckton, D. G. (2004) Pms2 is a genetic enhancer of trinucleotide CAG.CTG repeat somatic mosaicism: implications for the mechanism of triplet repeat expansion. Hum. Mol. Genet. 13, 1815-1825 https://doi.org/10.1093/hmg/ddh186
  9. Jakupciak, J. P. and Wells, R. D. (2000) Gene conversion (recombination) mediates expansions of $CTG{\cdot}CAG$ repeats. J. Biol. Chem. 275, 40003-40013 https://doi.org/10.1074/jbc.M007153200
  10. Kang, S., Ohshima, K., Jaworski, A., and Wells, R. D. (1996) CTG triplet repeats from the myotonic dystrophy gene are expanded in Escherichia coli distal to the replication origin as a single large event. J. Mol. Biol. 258, 543-547 https://doi.org/10.1006/jmbi.1996.0266
  11. Kim, S. J., Shon, B. H., Kang, J. H., Hahm, K. S., Yoo, O. J., et al. (1997) Cloning of novel trinucleotide-repeat (CAG) containing genes in mouse brain. Biochem. Biophys. Res. Commun. 240, 239-243 https://doi.org/10.1006/bbrc.1997.7643
  12. MacDougall, C. N., Clyde, D., Wood, T., Todman, M., Harbison, D., et al. (1999) Sex-specific transcripts of the Dstpk61 serine/ threonine kinase gene in Drosophila melanogaster. Eur. J. Biochem. 262, 456-466 https://doi.org/10.1046/j.1432-1327.1999.00404.x
  13. Masino, L., Nicastro, G., Menon, R. P., Dal Piaz, F., Calder, L., et al. (2004) Characterization of the structure and the amyloidogenic properties of the Josephin domain of the polyglutamine- containing protein ataxin-3. J. Mol. Biol. 344, 1021-1035 https://doi.org/10.1016/j.jmb.2004.09.065
  14. Nair, R., Carter, P., and Rost, B. (2003) NLSdb: database of nuclear localization signals. Nucleic Acids Res. 31, 397-399 https://doi.org/10.1093/nar/gkg001
  15. Napierala, M., Parniewski, P., Pluciennik, A., and Wells, R. D. (2002) Long CTG CAG repeat sequences markedly stimulate intramolecular recombination. J. Biol. Chem. 277, 34087-34100 https://doi.org/10.1074/jbc.M202128200
  16. Nucifora, F. C., Jr., Ellerby, L. M., Wellington, C. L., Wood, J. D., Herring, W. J., et al. (2003) Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity. J. Biol. Chem. 278, 13047-13055 https://doi.org/10.1074/jbc.M211224200
  17. Park, Y., Hong, S., Kim, S. J., and Kang, S. (2005) Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product. Mol. Cells 19, 23-30
  18. Paulson, H. L. and Fischbeck, K. H. (1996) Trinucleotide repeats in neurogenetic disorders. Annu. Rev. Neurosci. 19, 79-107 https://doi.org/10.1146/annurev.ne.19.030196.000455
  19. Reddy, P. S. and Housman, D. E. (1997) The complex pathology of trinucleotide repeats. Curr. Opin. Cell Biol. 9, 364-372 https://doi.org/10.1016/S0955-0674(97)80009-9
  20. Scherzinger, E., Sittler, A., Schweiger, K., Heiser, V., Lurz, R., et al. (1999) Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington's disease pathology. Proc. Natl. Acad. Sci. USA 96, 4604-4609
  21. Sobczak, K. and Krzyzosiak, W. J. (2005) CAG repeats containing CAA interruptions form branched hairpin structures in spinocerebellar ataxia type 2 transcripts. J. Biol. Chem. 280, 3898-3910 https://doi.org/10.1074/jbc.M409984200
  22. Stallings, R. L. (1994) Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence: implications for human genetic diseases. Genomics 21, 116-121 https://doi.org/10.1006/geno.1994.1232
  23. Strong, T. V., Tagle, D. A., Valdes, J. M., Elmer, L. W., Boehm, K., et al. (1993) Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues. Nat. Genet. 5, 259-265 https://doi.org/10.1038/ng1193-259
  24. Tompa, P. (2003) Intrinsically unstructured proteins evolve by repeat expansion. Bioessays 25, 847-855 https://doi.org/10.1002/bies.10324
  25. Watase, K., Weeber, E. J., Xu, B., Antalffy, B., Yuva-Paylor, L., et al. (2002) A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron 34, 905-919 https://doi.org/10.1016/S0896-6273(02)00733-X
  26. Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520-562 https://doi.org/10.1038/nature01262
  27. Wharton, K. A., Yedvobnick, B., Finnerty, V. G., and ArtavanisTsakonas, S. (1985) opa: a novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in D. melanogaster. Cell 40, 55-62 https://doi.org/10.1016/0092-8674(85)90308-3
  28. Zoghbi, H. Y. and Orr, H. T. (2000) Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23, 217-247 https://doi.org/10.1146/annurev.neuro.23.1.217