Summary
We examined the expression of dystrophin by immunohistochemical and immunoblot analyses in the skeletal and cardiac muscles of Xmdx/X+ heterozygous mice, which were obtained by mating male mdx mice (Xmdx/Y) with female wild type mice (X+/X+). Dystrophin was expressed on the surface membrane in both muscles, but the mode of expression was different between the two muscles. In cardiac muscle, dystrophin positive and negative cells were present in roughly equal numbers intermingled in a mosaic pattern; this was considered to reflect the random inactivation of X-chromosomes in early development. In skeletal muscle, most of the surface membrane was dystrophin positive. There were little signs of fiber necrosis or regeneration, and serum creatine kinase levels were normal. We are at present of opinion that the predominance of dystrophin-positive area in skeletal muscle is due to intracellular diffusion of dystrophin.
Similar content being viewed by others
References
Arahata K, Ishiura S, Ishiguro T, Tsukahara T, Suhara Y, Eguchi C, Ishihara T, Nonaka I, Ozawa E, Sugita H (1988) Immunostaining of skeletal and cardiac surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature 333:861–863
Arahata K, Ishihara T, Kamakura K, Tsukahara T, Ishiura S, Baba C, Matsumoto T, Nonaka I, Sugita H (1989a) Dystrophin and Duchenne's muscular dystrophy. Nature 321:398–399
Arahata K, Hoffman EP, Kunkel LM, Ishiura S, Tsukahara T, Ishihara T, Sunohara N, Nonaka I, Ozawa E, Sugita H (1989b) Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses. Proc Natl Acad Sci USA 86:7154–7158
Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviati IG, Di-Mauro S, Kunkel LM, Hoffman EP, Rowland LP (1988) Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 54:447–452
Cooper AR, Kurkinen M, Taylor A, Hogan BLM (1981) Studies on the biosynthesis of laminin by murine parietal endoderm cells. Eur J Biochem 119:189–197
Frair PM, Peterson AC (1983) The nuclear-cytoplasmic relationship in ‘mosaic’ skeletal muscle fibers from mouse chimeras. Exp Cell Res 145:167–178
Gartler SM, Riggs AD (1983) Mammalian X-chromosome inactivation. Ann Rev Genet 17:155–190
Hagiwara Y, Yoshida M, Nonaka I, Ozawa E (1989) Developmental expression of dystrophin on the plasma membrane of rat muscle cells. Protoplasma 151:11–18
Hoffman EP, Brown RH Jr, Kunkel LM (1987a) Dystrophin: the protein product of the Duchenne muscular dystrophy gene. Cell 51:919–928
Hoffman EP, Kundson CM, Campbell KP, Kunkel LM (1987b) Subcellular fractionation of dystrophin to the triad of skeletal muscle. Nature 330:754–758
Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey CT, Shapiro F, Kunkel LM (1988) Characterization of dystrophin in muscle biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N England J Med 318:1363–1368
Hurko O, McKee L, Zuurveld J, Swick HM (1987) Comparison of Duchenne and normal myoblasts from a heterozygote. Neurology 37:675–681
Ishikawa H (1966) Electron microscopic observations of satellite cells with special reference to the development of mammalian skeletal muscles. Z Anat Entwicklungsgesch 125:43–63
Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–228
Kundson CM, Hoffman EP, Kahl SD, Kunkel LM, Campbell KP (1988) Evidence for the association of dystrophin with the transverse tubular system in skeletal muscle. J Biol Chem 263:8480–8484
Lev AA, Feener CC, Kunkel LM, Brown RH Jr (1987) Expression of the Duchenne's muscular dystrophy gene in cultured muscle cells. J Biol Chem 262:15817–15820
Love DR, Hill DF, Dickson G, Spurr NK, Byth BC, Marsden RF, Walsh FS, Edwards YH, Davies KE (1989) An autosomal transcript in skeletal muscle with homology to dystrophin. Nature 339:55–58
Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373
Lyon MF (1972) X-chromosome inactivation and developmental patterns in mammals. Biol Rev 47:1–35
Monc M, Harper MI (1979) Sequential X-chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature 281:311–313
Moss FP, Leblond CP (1971) Satellite cells as the source of nuclei in muscles of growing rats. Anat Rec 170:421–436
Nudel U, Robzyc K, Yaffe D (1988) Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain. Nature 331:635–638
Oronzi Scott M, Sylvester JE, Heilman-Patterson T, Shi Y-J, Fieles W, Stedman H, Burghes A, Ray P, Worton R, Fischbeck KH (1988) Duchenne muscular dystrophy gene expression in normal and diseased human muscle. Science 239:1418–1420
Scinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244:1578–1580
Shimizu T, Matsumura K, Hashimoto K, Mannen T, Ishiguro T, Eguchi C, Nonaka I, Yoshida M, Ozawa E (1988) A monoclonal antibody to a synthetic polypeptide fragment of dystrophin (amino acid sequence from position 215 to 264). Proc Jpn Acad 64b:205–208
Stockdale FE, Holtzer H (1961) DNA synthesis and myogenesis. Exp Cell Res 24:508–520
Sugita H, Arahata K, Ishiguro T, Suhara Y, Tsukahara T, Ishiura S, Eguchi C, Nonaka I, Ozawa E (1988) Negative immunostaining of Duchenne muscular dystrophy (DMD) and mdx muscle surface membrane with antibody against synthetic peptide fragment predicted from DMD cDNA. Proc Jpn Acad 64b:37–39
Tanabe Y, Esaki K, Nomura T (1986) Skeletal muscle pathology in X-chromosome linked muscular dystrophy (mdx) mouse. Acta Neuropathol (Berl) 69:91–95
Tanaka H, Yoshida M, Ishiguro T, Eguchi C, Nonaka I, Ozawa E (1989a) Expression of dystrophin of the cell surface membrane of intrafusal fibers of human skeletal muscle. Protoplasma (in press)
Tanaka H, Shimizu T, Ozawa E (1989b) Expression of a dystrophin-like protein on the surface membrane of skeletal muscle fibers in mdx mice. Proc Jpn Acad 65 (B) 238–241
Watkins SC, Hoffman EP, Slayter HS, Kunkel LM (1988) Immunoelectron microscopic localization of dystrophin in myoblasts. Nature 333:863–866
Zubrzycka-Gaarn EE, Bulman DE, Karpati G, Burghes AHM, Belfall B, Klamut HJ, Talbot J, Hodges RS, Ray PN, Worton RG (1988) The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 333:466–469
Author information
Authors and Affiliations
Additional information
On leave from The Department of Pediatrics, Tokyo Women's Medical College
Rights and permissions
About this article
Cite this article
Tanaka, H., Ikeya, K. & Ozawa, E. Difference in the expression pattern of dystrophin on the surface membrane between the skeletal and cardiac muscles of mdx carrier mice. Histochemistry 93, 447–452 (1990). https://doi.org/10.1007/BF00266399
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00266399