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An alternative dystrophin transcript specific to peripheral nerve

Abstract

Transcription of the 2.5 megabase dystrophin gene gives rise to multiple isoforms. We describe a 5.2 kilobase transcript, expressed specifically in peripheral nerve, that initiates at a previously unrecognized exon located 850 basepairs upstream of dystrophin exon 56. The likely product of this transcript (Dp116) is detected by C–terminal dystrophin antibodies exclusively in peripheral nerve and cultured Schwann cells. Dp116 is located along the Schwann cell membrane but is not present in the compact myelin lamellae or in axons. Dp116 lacks actin–binding and spectrin–like rod domains, arguing that it functions differently in the Schwann cell than does the major dystrophin transcript in muscle.

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References

  1. Monaco, A.P. & Kunkel, L.M. Cloning of the Duchene/Becker muscular dystrophy locus. Adv. hum. Genet. 17, 61–98 (1988).

    CAS  PubMed  Google Scholar 

  2. Worton, R.G. & Thompson, M.W. Genetics of Duchenne muscular dystrophy. Ann. Rev. Genet. 22, 601–629 (1988).

    CAS  Article  PubMed  Google Scholar 

  3. Bar, S. et al. A novel product of the Duchenne muscular dystrophy gene which greatly differs from the known isoforms in its structure and tissue distribution. Biochem. J. 272, 557–560 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Lederfein, D. et al. A 71-Kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. Proc. natn. Acad. Sci. U.S.A. 89, 5346–5350 (1992).

    CAS  Article  Google Scholar 

  5. Blake, D.J. et al. Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Hum. molec. Genet. 1, 103–109 (1992).

    CAS  Article  PubMed  Google Scholar 

  6. Hugnot, J.P. et al. Distal transcript of the dystrophin gene initiated from an alternative first exon and encoding a 75-kDa protein widely distributed in nonmuscle tissues. Proc. natn. Acad. Sci. U.S.A. 89, 7506–7510 (1992).

    CAS  Article  Google Scholar 

  7. Feener, C.A., Koenig, M. & Kunkel, L.M. Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus. Nature 338, 509–511 (1989).

    CAS  Article  PubMed  Google Scholar 

  8. Nudel, U. et al. Duchenne muscular dystrophy gene product is not identical in muscle and brain. Nature 337, 76–78 (1989).

    CAS  Article  PubMed  Google Scholar 

  9. Chelly, J. et al. Dystrophin gene transcribed from different promoters in neuronal and glial cells. Nature 344, 64–65 (1990).

    CAS  Article  PubMed  Google Scholar 

  10. Klamut, H.J., Gangopadhyay, S.B., Worton, R.G. & Ray, P.N. Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene. Molec. cell. Biol. 10, 193–205 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Rapaport, D. et al. Characterization and cell type distribution of a novel, major transcript of the Duchenne Muscular Dystrophy gene. Differentiation 49, 187–193 (1992).

    CAS  Article  PubMed  Google Scholar 

  12. Gorecki, D.C. et al. Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. Hum. molec. Genet. 1, 505–510 (1992).

    CAS  Article  PubMed  Google Scholar 

  13. Chelly, J., Kaplan, J.C., Maire, P., Gautron, S. & Kahn, A. Transcription of the dystrophin gene in human muscle and non-muscle tissue. Nature 333, 858–860 (1988).

    CAS  Article  PubMed  Google Scholar 

  14. Samitt, C.E. & Bonilla, E. Immunocytochemical study of dystrophin at the myotendinous junction. Muscle Nerve 13, 493–500 (1990).

    CAS  Article  PubMed  Google Scholar 

  15. Miike, T., Miyatake, M., Zhao, J., Yoshioka, K. & Uchino, M. Immunohistochemical dystrophin reaction in synaptic regions. Brain Dev. 11, 344–346 (1989).

    CAS  Article  PubMed  Google Scholar 

  16. Shimizu, T., Matsumura, K., Sunada, Y. & Mannen, T. Dense immunostainings on both neuromuscular and myotendon junctions with an anti-dystrophin monoclonal antibody. Biomed. Res. 10, 405–409 (1989).

    CAS  Article  Google Scholar 

  17. Lidov, H.G.W., Byers, T.J., Watkins, S.C. & Kunkel, L.M. Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons. Nature 348, 725–728 (1990).

    CAS  Article  PubMed  Google Scholar 

  18. Miyatake, M. et al. Dystrophin: localization and presumed function. Muscle Nerve 14, 113–119 (1991).

    CAS  Article  PubMed  Google Scholar 

  19. Byers, T.J., Kunkel, L.M. & Watkins, S.C. The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle. J. cell Biol. 115, 411–421 (1991).

    CAS  Article  PubMed  Google Scholar 

  20. Hoffman, E.P., Hudecki, M.S., Rosenberg, P.A., Pollina, C.M. & Kunkel, L.M. Cell and fiber-type distribution of dystrophin. Neuron 1, 411–420 (1988).

    CAS  Article  PubMed  Google Scholar 

  21. Koenig, M. et al. Complete cloning of the Duchenne muscular dystrophy(DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50, 509–517 (1987).

    CAS  Article  PubMed  Google Scholar 

  22. Koenig, M., Monaco, A.P. & Kunkel, L.M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53, 219–226 (1988).

    CAS  Article  PubMed  Google Scholar 

  23. Koenig, M. et al. The molecular basis for Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion. Am. J. hum. Genet. 45, 498–506 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Monaco, A.P., Bertelson, C.J., Colletti Feener, C. & Kunkel, L.M. Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. Hum. Genet. 75, 221–227 (1987).

    CAS  Article  PubMed  Google Scholar 

  25. Mount, S.M. A catalogue of splice junction sequences. Nucl. Acids Res. 10, 459–472 (1983).

    Article  Google Scholar 

  26. Sicinski, P. et al. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244, 1578–1580 (1989).

    CAS  Article  PubMed  Google Scholar 

  27. Bennett, V. Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm. Physiol. Rev. 70, 1029–1065 (1990).

    CAS  Article  PubMed  Google Scholar 

  28. Ervasti, J.M. & Campbell, K.P. Membrane organization of the dystrophin-glycoprotein complex. Cell 66, 1121–1131 (1991).

    CAS  Article  PubMed  Google Scholar 

  29. Suzuki, A., Yoshida, M., Yamamoto, H. & Ozawa, E. Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. FEBS Lett. 308, 154–160 (1992).

    CAS  Article  PubMed  Google Scholar 

  30. Ibraghimov-Beskrovnaya, O. et al. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature 355, 696–702 (1992).

    CAS  Article  PubMed  Google Scholar 

  31. Arahata, K. et al. Preservation of the C-terminus of dystrophin molecule in the skeletal muscle from Becker muscular dystrophy. J. neurol. Sci. 101, 148–156 (1991).

    CAS  Article  PubMed  Google Scholar 

  32. Hoffman, E.P. et al. Is the carboxyl-terminus of dystrophin required for membrane association? A novel, severe case of Duchenne muscular dystrophy. Ann. Neurol. 30, 605–610 (1991).

    CAS  Article  PubMed  Google Scholar 

  33. Helliwell, T.R., Ellis, J.M., Mountford, R.C., Appleton, R.E. & Morris, G.E. A truncated dystrophin lacking the C-terminal domain is localized at the muscle membrane. Am. J. hum. Genet. 50, 508–514 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Recan, D. et al. Are cysteine-rich and COOH-terminal domains of dystrophin critical for sarcolemmal localization? J. clin. Invest. 89, 712–716 (1992).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Loh, E.Y., Elliott, J.F., Cwirla, S., Lanier, L.L. & Davis, M. Polymerase chain reaction with single-sided specificity: Analysis of T cell receptor delta chain. Science 243, 217–220 (1989).

    CAS  Article  PubMed  Google Scholar 

  36. Monaco, A.P. et al. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323, 646–650 (1986).

    CAS  Article  PubMed  Google Scholar 

  37. Byers, T.J., Neumann, P.E., Beggs, A.H. & Kunkel, L.M. ELISA quantitation of dystrophin for the diagnosis of Duchenne and Becker muscular dystrophies. Neurology 42, 570–576 (1992).

    CAS  Article  PubMed  Google Scholar 

  38. Coffey, A.J. et al. Construction of a 2.6-Mb contig in yeast artificial chromosomes spanning the human dystrophin gene using an STS-based approach. Genomics 12, 474–484 (1992).

    CAS  Article  PubMed  Google Scholar 

  39. Roberts, R.G., Coffey, A.J., Bobrow, M. & Bentley, D.R. Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR. Genomics 13, 942–950 (1992).

    CAS  Article  PubMed  Google Scholar 

  40. Koenig, M. & Kunkel, L.M. Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility. J. biol. Chem. 265, 4560–4566 (1990).

    CAS  PubMed  Google Scholar 

  41. Hemmings, L., Kuhlman, P.A. & Critchley, D.R. Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain. J. cell Biol. 116, 1369–1380 (1992).

    CAS  Article  PubMed  Google Scholar 

  42. Scott, M.O. et al. Duchenne muscular dystrophy gene expression in normal and diseased human muscle. Science 239, 1418–1420 (1988).

    CAS  Article  PubMed  Google Scholar 

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Byers, T., Lidov, H. & Kunkel, L. An alternative dystrophin transcript specific to peripheral nerve. Nat Genet 4, 77–81 (1993). https://doi.org/10.1038/ng0593-77

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