Brain, Vol. 110, No. 2, 269-299, 1987
© 1987 Oxford University Press
research-article |
THE MUTANT mdx: INHERITED MYOPATHY IN THE MOUSE
MORPHOLOGICAL STUDIES OF NERVES, MUSCLES AND END-PLATES
From the Department of Neuropathology, Institute of Neurology, The National Hospital, Queen Square, London
Correspondence to:
Correspondence to: Professor L. W. Duchen, Department of neuropathlogy, Institute of neurology, The National Hospital, Queen Square, London WCIN 3BG.
The mdx mutant mouse was first observed during a survey of genetic variations of pyruvate kinase in the mouse. Affected mice have high serum levels of this enzyme and although showing little disability they have widespread and severe muscle disease. Light and electron microscopy, muscle enzyme histo–chemistry and combined cholinesterase–silver impregnations were used for the study of affected and control animals aged 1day to 1 year. An early ultrastructural abnormality present already at 1 day was scattered focal streaming of Z-lines. Later there was also segmental muscle fibre necrosis and regeneration. The proportion of muscle fibres showing either necrosis, regeneration or internal nuclei was assessed in several muscles, at ages ranging from 10 days to 1 year. Acute segmental necrosis and regeneration were most marked at 1 to 2 months, although they were present at all ages. The number of fibres with internal nuclei increased progressively until 3 months when 70–80% showed this abnormality. Nerve terminals were unaffected but there was a reduction in the number and depth of post-synaptic folds at motor end-plates in adult animals, confirmed by morphometric analysis. Quantitative study of L4 motor root and tibial nerve showed that fibre numbers, axonal calibres and myelin sheath thickness were normal at all ages. No qualitative abnormalities were found in the CNS or other organs. The findings strongly suggest that the mdx mutant has a primary muscle disease and that the nervous system is normal.
Received April 8, 1986. Revised June 3, 1986. Accepted June 24, 1986.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Giacomotto, C. Pertl, C. Borrel, M. C. Walter, S. Bulst, B. Johnsen, D. L. Baillie, H. Lochmuller, C. Thirion, and L. Segalat Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy Hum. Mol. Genet., November 1, 2009; 18(21): 4089 - 4101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marotta, C. Ruiz-Roig, Y. Sarria, J. L. Peiro, F. Nunez, J. Ceron, F. Munell, and M. Roig-Quilis Muscle genome-wide expression profiling during disease evolution in mdx mice Physiol Genomics, April 10, 2009; 37(2): 119 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Chamberlain, J. Metzger, M. Reyes, D. Townsend, and J. A. Faulkner Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma FASEB J, July 1, 2007; 21(9): 2195 - 2204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Tidball and M. Wehling-Henricks The role of free radicals in the pathophysiology of muscular dystrophy J Appl Physiol, April 1, 2007; 102(4): 1677 - 1686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Slater, P. R. W. Fawcett, T. J. Walls, P. R. Lyons, S. J. Bailey, D. Beeson, C. Young, and D. Gardner-Medwin Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'. Brain, August 1, 2006; 129(Pt 8): 2061 - 2076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ito, S. Kimura, S. Ozasa, M. Matsukura, M. Ikezawa, K. Yoshioka, H. Ueno, M. Suzuki, K. Araki, K.-i. Yamamura, et al. Smooth muscle-specific dystrophin expression improves aberrant vasoregulation in mdx mice Hum. Mol. Genet., July 15, 2006; 15(14): 2266 - 2275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiao, A. Fond, B. Deng, M. Wehling-Henricks, M. E. Adams, S. C. Froehner, and J. G. Tidball Defects in neuromuscular junction structure in dystrophic muscle are corrected by expression of a NOS transgene in dystrophin-deficient muscles, but not in muscles lacking {alpha}- and {beta}1-syntrophins Hum. Mol. Genet., September 1, 2004; 13(17): 1873 - 1884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Iwata, Y. Katanosaka, Y. Arai, K. Komamura, K. Miyatake, and M. Shigekawa A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel J. Cell Biol., June 9, 2003; 161(5): 957 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Q. Harper, R. W. Crawford, C. DelloRusso, and J. S. Chamberlain Spectrin-like repeats from dystrophin and {alpha}-actinin-2 are not functionally interchangeable Hum. Mol. Genet., August 1, 2002; 11(16): 1807 - 1815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsuchiya, K. Kobayashi, T. Sakairi, K. Goto, M. Okada, F. Sano, J. Sugimoto, T. Morohashi, T. Usui, and M. Mutai Skeletal Myopathy in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene Toxicol Pathol, June 1, 2002; 30(4): 501 - 506. [Abstract] [PDF]
|
|
|
|
|
|
L. E. Warner, C. DelloRusso, R. W. Crawford, I. N. Rybakova, J. R. Patel, J. M. Ervasti, and J. S. Chamberlain Expression of Dp260 in muscle tethers the actin cytoskeleton to the dystrophin-glycoprotein complex and partially prevents dystrophy Hum. Mol. Genet., May 1, 2002; 11(9): 1095 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Blake, A. Weir, S. E. Newey, and K. E. Davies Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle Physiol Rev, April 1, 2002; 82(2): 291 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Culligan, N. Banville, P. Dowling, and K. Ohlendieck Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle J Appl Physiol, February 1, 2002; 92(2): 435 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson, S. I. Head, C. Rae, and J. W. Morley Brain function in Duchenne muscular dystrophy Brain, January 1, 2002; 125(1): 4 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ahmad, M. Brinson, B.L. Hodges, J.S. Chamberlain, and A. Amalfitano Mdx mice inducibly expressing dystrophin provide insights into the potential of gene therapy for Duchenne muscular dystrophy Hum. Mol. Genet., October 1, 2000; 9(17): 2507 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Crawford, J. A. Faulkner, R. H. Crosbie, K. P. Campbell, S. C. Froehner, and J. S. Chamberlain Assembly of the Dystrophin-Associated Protein Complex Does Not Require the Dystrophin Cooh-Terminal Domain J. Cell Biol., September 18, 2000; 150(6): 1399 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Rafael, E. R. Townsend, S. E. Squire, A. C. Potter, J. S. Chamberlain, and K. E. Davies Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure Hum. Mol. Genet., May 22, 2000; 9(9): 1357 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Williams and R. J. Bloch Extensive but Coordinated Reorganization of the Membrane Skeleton in Myofibers of Dystrophic (mdx) Mice J. Cell Biol., March 22, 1999; 144(6): 1259 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mokhtarian, J. P. Lefaucheur, P. C. Even, and A. Sebille Hindlimb immobilization applied to 21-day-old mdx mice prevents the occurrence of muscle degeneration J Appl Physiol, March 1, 1999; 86(3): 924 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Megeney, B. Kablar, R. L. S. Perry, C. Ying, L. May, and M. A. Rudnicki Severe cardiomyopathy in mice lacking dystrophin and MyoD PNAS, January 5, 1999; 96(1): 220 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Xu and M. M. Salpeter Acetylcholine Receptors in Innervated Muscles of Dystrophic mdx Mice Degrade as after Denervation J. Neurosci., November 1, 1997; 17(21): 8194 - 8200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Grady, J. P. Merlie, and J. R. Sanes Subtle Neuromuscular Defects in Utrophin-deficient Mice J. Cell Biol., February 24, 1997; 136(4): 871 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Deconinck, A. C. Potter, J. M. Tinsley, S. J. Wood, R. Vater, C. Young, L. Metzinger, A. Vincent, C. R. Slater, and K. E. Davies Postsynaptic Abnormalities at the Neuromuscular Junctions of Utrophin-deficient Mice J. Cell Biol., February 24, 1997; 136(4): 883 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tidball, D. Albrecht, B. Lokensgard, and M. Spencer Apoptosis precedes necrosis of dystrophin-deficient muscle J. Cell Sci., January 6, 1995; 108(6): 2197 - 2204. [Abstract] [PDF]
|
|
|
|
|
|
D. Law, D. Allen, and J. Tidball Talin, vinculin and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosis J. Cell Sci., January 6, 1994; 107(6): 1477 - 1483. [Abstract] [PDF]
|
|
|
|
|
|
I Guillet-Deniau, A Leturque, and J Girard Expression and cellular localization of glucose transporters (GLUT1, GLUT3, GLUT4) during differentiation of myogenic cells isolated from rat foetuses J. Cell Sci., January 3, 1994; 107(3): 487 - 496. [Abstract] [PDF]
|
|
|
|
|
|
H. B. Peng and Q. Chen Induction of dystrophin localization in cultured Xenopus muscle cells by latex beads J. Cell Sci., October 1, 1992; 103(2): 551 - 563. [Abstract] [PDF]
|
|
|
|
 |
|
 P Sicinski, Y Geng, A. Ryder-Cook, E. Barnard, M. Darlison, and P. Barnard The molecular basis of muscular dystrophy in the mdx mouse: a point mutation Science, June 30, 1989; 244(4912): 1578 - 1580. [Abstract] [PDF]
|
|
|
|
|
|
J DiMario, N Buffinger, S Yamada, and R. Strohman Fibroblast growth factor in the extracellular matrix of dystrophic (mdx) mouse muscle Science, May 12, 1989; 244(4905): 688 - 690. [Abstract] [PDF]
|
|