Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1992 Nov 2;119(4):811–821. doi: 10.1083/jcb.119.4.811

Localization of dystrophin gene transcripts during mouse embryogenesis

PMCID: PMC2289682  PMID: 1429837

Abstract

The spatial and temporal expression of the dystrophin gene has been examined during mouse embryogenesis, using in situ hybridization on tissue sections with a probe from the 5' end of the dystrophin coding sequence. In striated muscle, dystrophin transcripts are detectable from about 9 d in the heart and slightly later in skeletal muscle. However, there is an important difference between the two types of muscle: the heart is already functional as a contractile organ before the appearance of dystrophin transcripts, whereas this is not the case in skeletal muscle, where dystrophin and myosin heavy chain transcripts are first detectable at the same time. In the heart, dystrophin transcripts accumulate initially in the outflow tract and, at later stages, in both the atria and ventricles. In skeletal muscle, the gene is expressed in all myocytes irrespective of fiber type. In smooth muscle dystrophin transcripts are first detectable from 11 d post coitum in blood vessels, and subsequently in lung bronchi and in the digestive tract. The other major tissue where the dystrophin gene is expressed is the brain, where transcripts are clearly detectable in the cerebellum from 13 d. High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context. The findings are discussed in the context of the pathology of Duchenne muscular dystrophy.

Full Text

The Full Text of this article is available as a PDF (5.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bar S., Barnea E., Levy Z., Neuman S., Yaffe D., Nudel U. A novel product of the Duchenne muscular dystrophy gene which greatly differs from the known isoforms in its structure and tissue distribution. Biochem J. 1990 Dec 1;272(2):557–560. doi: 10.1042/bj2720557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnea E., Zuk D., Simantov R., Nudel U., Yaffe D. Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells. Neuron. 1990 Dec;5(6):881–888. doi: 10.1016/0896-6273(90)90348-j. [DOI] [PubMed] [Google Scholar]
  3. Bies R. D., Phelps S. F., Cortez M. D., Roberts R., Caskey C. T., Chamberlain J. S. Human and murine dystrophin mRNA transcripts are differentially expressed during skeletal muscle, heart, and brain development. Nucleic Acids Res. 1992 Apr 11;20(7):1725–1731. doi: 10.1093/nar/20.7.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bober E., Lyons G. E., Braun T., Cossu G., Buckingham M., Arnold H. H. The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development. J Cell Biol. 1991 Jun;113(6):1255–1265. doi: 10.1083/jcb.113.6.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buckingham M. Making muscle in mammals. Trends Genet. 1992 Apr;8(4):144–148. doi: 10.1016/0168-9525(92)90373-C. [DOI] [PubMed] [Google Scholar]
  6. Bulfield G., Siller W. G., Wight P. A., Moore K. J. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189–1192. doi: 10.1073/pnas.81.4.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Byers T. J., Kunkel L. M., Watkins S. C. The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle. J Cell Biol. 1991 Oct;115(2):411–421. doi: 10.1083/jcb.115.2.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chamberlain J. S., Farwell N. J., Chamberlain J. R., Cox G. A., Caskey C. T. PCR analysis of dystrophin gene mutation and expression. J Cell Biochem. 1991 Jul;46(3):255–259. doi: 10.1002/jcb.240460309. [DOI] [PubMed] [Google Scholar]
  9. Chamberlain J. S., Pearlman J. A., Muzny D. M., Gibbs R. A., Ranier J. E., Caskey C. T., Reeves A. A. Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. Science. 1988 Mar 18;239(4846):1416–1418. doi: 10.1126/science.3347839. [DOI] [PubMed] [Google Scholar]
  10. Chelly J., Kaplan J. C., Maire P., Gautron S., Kahn A. Transcription of the dystrophin gene in human muscle and non-muscle tissue. Nature. 1988 Jun 30;333(6176):858–860. doi: 10.1038/333858a0. [DOI] [PubMed] [Google Scholar]
  11. Chelly J., Montarras D., Pinset C., Berwald-Netter Y., Kaplan J. C., Kahn A. Quantitative estimation of minor mRNAs by cDNA-polymerase chain reaction. Application to dystrophin mRNA in cultured myogenic and brain cells. Eur J Biochem. 1990 Feb 14;187(3):691–698. doi: 10.1111/j.1432-1033.1990.tb15355.x. [DOI] [PubMed] [Google Scholar]
  12. Clerk A., Strong P. N., Sewry C. A. Characterisation of dystrophin during development of human skeletal muscle. Development. 1992 Feb;114(2):395–402. doi: 10.1242/dev.114.2.395. [DOI] [PubMed] [Google Scholar]
  13. Cusella-De Angelis M. G., Lyons G., Sonnino C., De Angelis L., Vivarelli E., Farmer K., Wright W. E., Molinaro M., Bouchè M., Buckingham M. MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites. J Cell Biol. 1992 Mar;116(5):1243–1255. doi: 10.1083/jcb.116.5.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dickson G., Pizzey J. A., Elsom V. E., Love D., Davies K. E., Walsh F. S. Distinct dystrophin mRNA species are expressed in embryonic and adult mouse skeletal muscle. FEBS Lett. 1988 Dec 19;242(1):47–52. doi: 10.1016/0014-5793(88)80982-7. [DOI] [PubMed] [Google Scholar]
  15. Ervasti J. M., Campbell K. P. Membrane organization of the dystrophin-glycoprotein complex. Cell. 1991 Sep 20;66(6):1121–1131. doi: 10.1016/0092-8674(91)90035-w. [DOI] [PubMed] [Google Scholar]
  16. Ervasti J. M., Ohlendieck K., Kahl S. D., Gaver M. G., Campbell K. P. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature. 1990 May 24;345(6273):315–319. doi: 10.1038/345315a0. [DOI] [PubMed] [Google Scholar]
  17. Fardeau M., Tomé F. M., Collin H., Augier N., Pons F., Léger J., Léger J. Présence d'une protéine de type dystrophine au niveau de la jonction neuromusculaire dans la dystrophie musculaire de Duchenne et la souris mutante "mdx". C R Acad Sci III. 1990;311(5):197–204. [PubMed] [Google Scholar]
  18. Feener C. A., Koenig M., Kunkel L. M. Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus. Nature. 1989 Apr 6;338(6215):509–511. doi: 10.1038/338509a0. [DOI] [PubMed] [Google Scholar]
  19. Gilgenkrantz H., Hugnot J. P., Lambert M., Chafey P., Kaplan J. C., Kahn A. Positive and negative regulatory DNA elements including a CCArGG box are involved in the cell type-specific expression of the human muscle dystrophin gene. J Biol Chem. 1992 May 25;267(15):10823–10830. [PubMed] [Google Scholar]
  20. Gorecki D., Geng Y., Thomas K., Hunt S. P., Barnard E. A., Barnard P. J. Expression of the dystrophin gene in mouse and rat brain. Neuroreport. 1991 Dec;2(12):773–776. doi: 10.1097/00001756-199112000-00011. [DOI] [PubMed] [Google Scholar]
  21. Hoffman E. P., Hudecki M. S., Rosenberg P. A., Pollina C. M., Kunkel L. M. Cell and fiber-type distribution of dystrophin. Neuron. 1988 Jul;1(5):411–420. doi: 10.1016/0896-6273(88)90191-2. [DOI] [PubMed] [Google Scholar]
  22. Hoffman E. P., Kunkel L. M. Dystrophin abnormalities in Duchenne/Becker muscular dystrophy. Neuron. 1989 Jan;2(1):1019–1029. doi: 10.1016/0896-6273(89)90226-2. [DOI] [PubMed] [Google Scholar]
  23. Jasmin B. J., Cartaud A., Ludosky M. A., Changeux J. P., Cartaud J. Asymmetric distribution of dystrophin in developing and adult Torpedo marmorata electrocyte: evidence for its association with the acetylcholine receptor-rich membrane. Proc Natl Acad Sci U S A. 1990 May;87(10):3938–3941. doi: 10.1073/pnas.87.10.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jung D., Pons F., Léger J. J., Aunis D., Rendon A. Dystrophin in central nervous system: a developmental, regional distribution and subcellular localization study. Neurosci Lett. 1991 Mar 11;124(1):87–91. doi: 10.1016/0304-3940(91)90828-h. [DOI] [PubMed] [Google Scholar]
  25. Lidov H. G., Byers T. J., Watkins S. C., Kunkel L. M. Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons. Nature. 1990 Dec 20;348(6303):725–728. doi: 10.1038/348725a0. [DOI] [PubMed] [Google Scholar]
  26. Love D. R., Hill D. F., Dickson G., Spurr N. K., Byth B. C., Marsden R. F., Walsh F. S., Edwards Y. H., Davies K. E. An autosomal transcript in skeletal muscle with homology to dystrophin. Nature. 1989 May 4;339(6219):55–58. doi: 10.1038/339055a0. [DOI] [PubMed] [Google Scholar]
  27. Love D. R., Morris G. E., Ellis J. M., Fairbrother U., Marsden R. F., Bloomfield J. F., Edwards Y. H., Slater C. P., Parry D. J., Davies K. E. Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3243–3247. doi: 10.1073/pnas.88.8.3243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lyons G. E., Buckingham M. E., Mannherz H. G. alpha-Actin proteins and gene transcripts are colocalized in embryonic mouse muscle. Development. 1991 Feb;111(2):451–454. doi: 10.1242/dev.111.2.451. [DOI] [PubMed] [Google Scholar]
  29. Lyons G. E., Buckingham M. E., Tweedie S., Edwards Y. H. Carbonic anhydrase III, an early mesodermal marker, is expressed in embryonic mouse skeletal muscle and notochord. Development. 1991 Jan;111(1):233–244. doi: 10.1242/dev.111.1.233. [DOI] [PubMed] [Google Scholar]
  30. Lyons G. E., Mühlebach S., Moser A., Masood R., Paterson B. M., Buckingham M. E., Perriard J. C. Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle. Development. 1991 Nov;113(3):1017–1029. doi: 10.1242/dev.113.3.1017. [DOI] [PubMed] [Google Scholar]
  31. Lyons G. E., Ontell M., Cox R., Sassoon D., Buckingham M. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J Cell Biol. 1990 Oct;111(4):1465–1476. doi: 10.1083/jcb.111.4.1465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lyons G. E., Schiaffino S., Sassoon D., Barton P., Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990 Dec;111(6 Pt 1):2427–2436. doi: 10.1083/jcb.111.6.2427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Miranda A. F., Bonilla E., Martucci G., Moraes C. T., Hays A. P., Dimauro S. Immunocytochemical study of dystrophin in muscle cultures from patients with Duchenne muscular dystrophy and unaffected control patients. Am J Pathol. 1988 Sep;132(3):410–416. [PMC free article] [PubMed] [Google Scholar]
  34. Moser H. Duchenne muscular dystrophy: pathogenetic aspects and genetic prevention. Hum Genet. 1984;66(1):17–40. doi: 10.1007/BF00275183. [DOI] [PubMed] [Google Scholar]
  35. Ohlendieck K., Ervasti J. M., Matsumura K., Kahl S. D., Leveille C. J., Campbell K. P. Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle. Neuron. 1991 Sep;7(3):499–508. doi: 10.1016/0896-6273(91)90301-f. [DOI] [PubMed] [Google Scholar]
  36. Ontell M., Kozeka K. The organogenesis of murine striated muscle: a cytoarchitectural study. Am J Anat. 1984 Oct;171(2):133–148. doi: 10.1002/aja.1001710202. [DOI] [PubMed] [Google Scholar]
  37. Ott M. O., Bober E., Lyons G., Arnold H., Buckingham M. Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development. 1991 Apr;111(4):1097–1107. doi: 10.1242/dev.111.4.1097. [DOI] [PubMed] [Google Scholar]
  38. Sassoon D. A., Garner I., Buckingham M. Transcripts of alpha-cardiac and alpha-skeletal actins are early markers for myogenesis in the mouse embryo. Development. 1988 Sep;104(1):155–164. doi: 10.1242/dev.104.1.155. [DOI] [PubMed] [Google Scholar]
  39. Sassoon D., Lyons G., Wright W. E., Lin V., Lassar A., Weintraub H., Buckingham M. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature. 1989 Sep 28;341(6240):303–307. doi: 10.1038/341303a0. [DOI] [PubMed] [Google Scholar]
  40. Sealock R., Butler M. H., Kramarcy N. R., Gao K. X., Murnane A. A., Douville K., Froehner S. C. Localization of dystrophin relative to acetylcholine receptor domains in electric tissue and adult and cultured skeletal muscle. J Cell Biol. 1991 Jun;113(5):1133–1144. doi: 10.1083/jcb.113.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tanaka H., Ishiguro T., Eguchi C., Saito K., Ozawa E. Expression of a dystrophin-related protein associated with the skeletal muscle cell membrane. Histochemistry. 1991;96(1):1–5. doi: 10.1007/BF00266753. [DOI] [PubMed] [Google Scholar]
  42. Wessels A., Ginjaar I. B., Moorman A. F., van Ommen G. J. Different localization of dystrophin in developing and adult human skeletal muscle. Muscle Nerve. 1991 Jan;14(1):1–7. doi: 10.1002/mus.880140102. [DOI] [PubMed] [Google Scholar]
  43. Yeadon J. E., Lin H., Dyer S. M., Burden S. J. Dystrophin is a component of the subsynaptic membrane. J Cell Biol. 1991 Nov;115(4):1069–1076. doi: 10.1083/jcb.115.4.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yoshida M., Ozawa E. Glycoprotein complex anchoring dystrophin to sarcolemma. J Biochem. 1990 Nov;108(5):748–752. doi: 10.1093/oxfordjournals.jbchem.a123276. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES