What has the mdx mouse model of duchenne muscular dystrophy contributed to our understanding of this disease?

Journal of Muscle Research and Cell Motility

Volumn 36, Issue 2, 2015, Pages 155-167

  Manning, Jennifer ^a   O’Malley, Dervla ^a,b  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Calcium; Corticosteroids; Duchenne muscular dystrophy; Genetic therapy; Inflammation; Mdx mouse

Indexed keywords

ANIMAL; DISEASE MODEL; DUCHENNE MUSCULAR DYSTROPHY; GENETICS; HUMAN; METABOLISM; MOUSE; PATHOLOGY; PATHOPHYSIOLOGY; X CHROMOSOME LINKED MUSCULAR DYSTROPHIC MOUSE;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; MICE; MICE, INBRED MDX; MUSCULAR DYSTROPHY, DUCHENNE;

EID: 84939933269     PISSN: 01424319     EISSN: 15732657     Source Type: Journal    
DOI: 10.1007/s10974-015-9406-4     Document Type: Review

References (161)

1. Abdel-Salam E, Abdel-Meguid I, Korraa SS (2009) Markers of degeneration and regeneration in duchenne muscular dystrophy. Acta Myol 28(3):94–100
2. Abresch R, Seyden N, Wineinger M (1998) Quality of life. Issues for persons with neuromuscular diseases. Phys Med Rehabil Clin N Am 9(1):233–248
3. Andreetta F et al (2003) Immunomodulation of TGF-beta1 in mdx mouse inhibits connective tissue proliferation in diaphragm but increases inflammatory response: implications for antifibrotic therapy. J Neuroimmunol, 15(5), p. II
4. Anderson J, Weber M, Vargas C (2000) Deflazacort increases laminin expression and myogenic repair, and induces early persistant functional gain in mdx mouse muscular dystrophy. Cell Transpl 9(4):551–564
5. Aoki Y et al (2012) Bodywide skipping of exons 45–55 in dystrophic mdx52 mice by systemic antisense delivery. Proc Natl Acad Sci USA 109(34):13763–13768
6. Arakia E et al (1997) Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy. Biochem Biophys Res Commun 238(2):492–497
7. Archer JD, Vargas CC, Anderson JE (2006) Persistent and improved functional gain in mdx dystrophic mice after treatment with l-arginine and deflaxacort. FASEB J 24:1–24
8. Arechavala-Gomeza V et al (2010) Revertant fibres and dystrophin traces in duchenne muscular dystrophy: implication for clinical trials. Neuromuscul Disord 20(5):295–301
9. Asai A et al (2007) Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. PLoS ONE 2(8):e806
10. Baccari M et al (2007) Reversal by relaxin of altered ileal spontaneous contractions in dystrophic (mdx) mice through a nitric oxide-mediated mechanism. Am J Physiol—Regul, Integr Comp Physiol 293:R662–R668
11. Baltgalvis KA et al (2009) The effects of prednisolone on skeletal muscle contractility in mdx mice. Muscle Nerve 40(3):443–454
12. Barohn RJ et al (1988) Gastric hypomotility in duchenne’s muscular dystrophy. N Engl J Med 319:15–18
13. Barohn R, Amato A, Griggs R (1998) Overview of distal myopathies: from the clinical to the molecular. Neuromuscul Disord 8(5):309–316
14. Bates G et al (2013) Molecular, cellular, and muscle strip mechanics of the mdx mouse diaphragm. Am J Physiol Cell Physiol 304(9):C873–C880
15. Baydur A et al (1990) Decline in respiratory function and experience with long-term assisted ventilation in advanced duchenne’s muscular dystophy. Chest 97(4):884–889
16. Beck J et al (2006) Diaphragmatic function in advanced duchenne muscular dystrophy. Neuromuscul Disord 16:161–167
17. Bia B et al (1999) Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of duchenne muscular dystrophy. J Mol Cell Cardiol 31(10):1857–1862
18. Blake D, Tinsley J, Davies K (1996) Utrophin: a structural and functional comparison to dystrophin. Brain Pathol 6(1):37–47
19. Bonuccelli G et al (2003) Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am J Pathol 163(4):1663–1675
20. Borrelli O et al (2005) Evolution of gastric electrical features and gastric emptying in children with duchenne and becker muscular dystrophy. Am J Gastroenterol 100(3):695–702
21. Bothwell JE et al (2002) Duchenne muscular dystrophy-parental perceptions. Clin Pediatr 41(2):105–109
22. Brunelli S et al (2007) Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. Proc Natl Acad Sci USA 104(1):264–269
23. Bulfield G (1984) X chromosome-linked muscular dystrophy. Proc Natl Acad Sci USA 81:1189–1192
24. Byers TJ, Kunkel LM, Watkinst SC (1991) The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle. J cell Biol 115(2):411–421
25. Campbell K et al (2010) Revertant muscle fibers expressing dystrophin do not tolerize the immune system in duchenne muscular dystrophy: lessons learned from a Phase I clinical trial. J Immunol 184:96–99
26. Carlson CG, Samadi A, Siegel A (2005) Chronic treatment with agents that stabilize cytosolic IkappaB-alpha enhances survival and improves resting membrane potential in MDX muscle fibers subjected to chronic passive stretch. Neurobiol Dis 20(3):719–730
27. Cirak S et al (2011) Exon skipping and dystrophin restoration in patients with duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378(9791):595–605
28. Collins CA, Morgan JE (2003) Duchenne’s muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies. Int J Exp Pathol 84(4):165–172
29. Compton A et al (2005) The syntrophin-dystrobrevin subcomplex in human neuromuscular disorders. J Neuropathol Exp Neurol 64(4):350–361
30. Connor TJ, Leonard BE (1998) Depression, stress and immunological activation the role of cytokines in depressive disorders. Life Sci 62(7):583–606
31. Coulton G et al (1988) The mdx mouse skeletal muscle myopathy: II Contractile properties. Neuropathol Appl Neurobiol 14(4):299–314
32. Cozzoli A et al (2011) Evaluation of potential synergistic action of a combined treatment with alpha-methyl-prednisolone and taurine on the mdx mouse model of duchenne muscular dystrophy. Neuropathol Appl Neurobiol 37(3):243–256
33. Cros D et al (1989) Muscle hypertrophy in duchenne muscular dystrophy. J Neurol 236(1):43–47
34. Dangain J, Vrbova G (1984) Muscle development in mdx mutant mice. Muscle Nerve 7(9):700–704
35. Davies KE, Nowak KJ (2006) Molecular mechanisms of muscular dystrophies: old and new players. Nat Rev Mol Cell Biol 7(10):762–773
36. De Bruin P et al (1997) Diaphragm thickness and inspiratory strength in patients with duchenne muscular dystrophy. Thorax 52:472–475
37. Deconinck N, Dan B (2007) Pathophysiology of duchenne muscular dystrophy: current hypotheses. Pediatr Neurol 36(1):1–7
38. Deconinck AE et al (1997) Utrophin-dystrophin-deficient mice as a model for duchenne muscular dystrophy. Cell 90(4):717–727
39. Di Certo MG et al (2010) The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice. Hum Mol Genet 19(5):752–760
40. Dinan D et al (2003) Gastric wall weakening resulting in separate perforations in a patient with duchenne’ s muscular dystrophy. Am J Roentgenol 181:807–808
41. Du Y et al (2013) Sputum Interleukin-6, tumor necrosis factor-α and salivary cortisol as new biomarkers of depression in lung cancer patients. Progress Neuro-Psychopharmacol Biol Psychiatr 47:69–76
42. Duboc D et al (2007) Perindopril preventive treatment on mortality in duchenne muscular dystrophy 10 years’ follow-up. Am Heart J 154(3):596–602
43. Ebihara S et al (2000) Differential effects of dystrophin and utrophin gene transfer in immunocompetent muscular dystrophy (mdx) mice. Physiol Genomics 8(3):133–144
44. Engel WK, Hawley RJ (1977) Focal lesions of muscle in peripheral vascular disease. J Neurol 215(3):161–168
45. Ennen JP, Verma M, Asakura A (2013) Vascular-targeted therapies for duchenne muscular dystrophy. Skelet Muscle 3(9):1–12
46. Ervasti JM, Campbell KP (1991) Membrane organization of the dystrophin-glycoprotein complex. Cell 66(6):1121–1131
47. Fall AM et al (2006) Induction of revertant fibres in the mdx mouse using antisense oligonucleotides. Genetic Vaccines Ther 4:3
48. Fitzpatrick C, Barry C, Garvey C (1986) Psychiatric disorder among boys with duchenne muscular dystrophy. Dev Med Child Neurol 28(5):589–595
49. Fletcher S et al (2006) Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide. J Gene Med 8(2):207–216
50. Fong P et al (1990) Increased activity of calcium leak channels in myotubes of duchenne human and mdx mouse origin. Science 250(4981):673–676
51. Forbes SC et al (2014) Magnetic resonance imaging and spectroscopy assessment of lower extremity skeletal muscles in boys with Duchenne muscular dystrophy: a multicenter cross sectional study. PLoS ONE 9(9):e106435
52. Fraysse B et al (2004) The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo. Neurobiol Dis 17(2):144–154
53. Garrood P et al (2009) MR imaging in duchenne muscular dystrophy quantification of T1-weighted signal, contrast uptake, and the effects of exercise. J Magn Reson Imaging 30(5):1130–1138
54. Gehrig SM et al (2008) Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Exp Physiol 93(11):1190–1198
55. Gerber AR, Bale TL (2012) Antiinflammatory treatment ameliorates HPA stress axis dysfunction in a mouse model of stress sensitivity. Endocrinology 153(10):4830–4837
56. Gilbert RÉN et al (1999) Adenovirus-mediated utrophin gene transfer mitigates the dystrophic phenotype of mdx mouse muscles. Hum Gene Ther 10(8):1299–1310
57. Glaser R, Kiecolt-glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5:243–251
58. Goemans NM et al (2011) Systemic Administration of PRO051 in duchenne’s muscular dystrophy. New Engl J Med 364(16):1513–1522
59. Gosselin LE, Williams JE (2006) Pentoxifylline fails to attenuate fibrosis in dystrophic (mdx) diaphragm muscle. Muscle Nerve 33(6):820–823
60. Goyenvalle A et al (2004) Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Sci (N.Y.) 306(5702):1796–1799
61. Grange RW (2011) Green tea extract decreases muscle pathology and NF-κB immunostaining in regenerating muscle fibers of mdx mice. Clin Nutr 29(3):391–398
62. Gregorevic P et al (2006) rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med 12(7):787–789
63. Grounds MD et al (2008) Towards developing standard operating procedures for pre- clinical testing in the mdx mouse model of duchenne muscular dystrophy. Neurobiol Dis 31(1):1–19
64. Gumerson JD, Michele DE (2011) The dystrophin-glycoprotein complex in the prevention of muscle damage. J Biomed Biotechnol 2011:1–13
65. Heenskerk et al (2009) In vivo comparison of 2 -O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J Gene Med 11:257–266
66. Hoen PA t et al (2006) Gene expression profiling to monitor therapeutic and adverse effects of antisense therapies for duchenne muscular dystrophy. Pharmacogenomics 7(3):281–297
67. Hoffman EP et al (1990) Somatic reversion/suppression of the mouse mdx phenotype in vivo. J Neurol Sci 99(1):9–25
68. Huang P et al (2009) Imatinib attenuates skeletal muscle dystrophy in mdx mice. FASEB J 23(8):2539–2548
69. Ito K et al (2006) Smooth muscle-specific dystrophin expression improves aberrant vasoregulation in mdx mice. Hum Mol Genet 15(14):5–7
70. Jin RC, Loscalzo J (2010) Vascular nitric oxide: formation and function. J Blood Med 2010(1):147–162
71. Kaprielian RR et al (2000) Distinct patterns of dystrophin organization in myocyte sarcolemma and transverse tubules of normal and diseased human myocardium. Circulation 100:2586–2594
72. Keep NH (2000) Structural comparison of actin binding in utrophin and dystrophin. Neurological Sci 21(5 Suppl):S929–S937
73. Khairallah M et al (2007) Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy. J Mol Cell Cardiol 43(2):119–129
74. Kim J-H et al (2013) Contribution of oxidative stress to pathology in diaphragm and limb muscles with duchenne muscular dystrophy. J Muscle Res Cell Motil 34(1):1–13
75. Kostek M et al (2012) IL-6 signaling blockade increases inflammation but does not improve muscle function in the mdx mouse. BMC Musculoskelet Disord 13(1):106
76. Krag TOB et al (2004) Heregulin ameliorates the dystrophic phenotype in mdx mice. Proc Natl Acad Sci USA 101(38):13856–13860
77. Kumar A, Boriek AM (2003) Mechanical stress activates the nuclear factor-kappaB pathway in skeletal muscle fibers: a possible role in duchenne muscular dystrophy. FASEB J 17(3):386–396
78. Lapidos KA, Kakkar R, McNally EM (2004) The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res 94(8):1023–1031
79. Larcher T et al (2014) Characterization of dystrophin deficient rats: a new model for duchenne muscular dystrophy. PLoS ONE 9(10):e110371
80. Leon S et al (1986) Chronic intestinal pseudoobstruction as a complication of Duchenne’s muscular dystrophy. Gastroenterology 90(2):455–459
81. Leonard BE, Myint A (2006) Changes in the immune system in depression and dementia: causal or co-incidental effects? Diol Clin Neurosci 8(2):163–174
82. Lim J-H, Kim D-Y, Bang MS (2004) Effects of exercise and steroid on skeletal muscle apoptosis in the mdx mouse. Muscle Nerve 30(4):456–462
83. Love D et al (1989) An autosomal transcript in skeletal muscle with homology to dystrophin. Nature 339(6219):55–58
84. Lu QL et al (2003) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med 9(8):1009–1014
85. Lu QL et al (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci USA 102(1):198–203
86. Lu QL et al (2011) The status of exon skipping as a therapeutic approach to duchenne muscular dystrophy. Mol Ther 19(1):9–15
87. Maes M (2008) The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett 29(3):287–291
88. Malerba A et al (2009) Dosing regimen has a significant impact on the efficiency of morpholino oligomer-induced exon skipping in mdx mice. Hum Gene Ther 20(9):955–965
89. Malpass K (2012) Neuromuscular disease a novel imaging method to quantify low levels of dystrophin in duchenne muscular dystrophy. Nat Rev Neurol 8(120):120
90. Manning J et al (2014) Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of duchenne muscular dystrophy. Exp Physiol 99(10):1370–1386
91. Manzur A et al (2008) Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. (1):CD003725. doi:10.1002/14651858.CD003725.pub3.
92. Marques MJ et al (2009) Long-term therapy with deflazacort decreases myocardial fibrosis in mdx mice. Muscle Nerve 40(3):466–468
93. Matsumura K et al (1992) Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Nature 360(6494):588–591
94. Matsumura CY et al (2011) Stretch-activated calcium channel protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice. Am J Physiol Cell Physiol 301(6):C1344–C1350
95. Mendell JR et al (2013) Eteplirsen for the treatment of duchenne muscular dystrophy. Ann Neurol 74(5):637–647
96. Messina S et al (2009) Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone. Exp Neurol 220(2):349–358
97. Messina S et al (2011) Activation of NF-kappaB pathway in Duchenne muscular dystrophy: relation to age. Acta Myol 30(1):16–23
98. Michele DE, Campbell KP (2003) Dystrophin-glycoprotein complex: post-translational processing and dystroglycan function. J Biol Chem 278(18):15457–15460
99. Mizunoya W et al (2011) Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. Am J Physiol Cell Physiol 300(5):C1065–C1077
100. Moens P, Baatsen PH, Maréchal G (1993) Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch. J Muscle Res Cell Motil 14(4):446–451
101. Mok E et al (2009) Lack of functional benefit with glutamine versus placebo in duchenne muscular dystrophy: a randomized crossover trial. PLoS ONE 4(5):e5448
102. Mosqueira M et al (2013) Cardiac and respiratory dysfunction in duchenne muscular dystrophy and the role of second messengers. Med Res Revies 33(5):1174–1213
103. Mulè F, Amato A, Serio R (2010) Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice. J Physiol Sci 60(1):75–79
104. Nakae Y et al (2008) Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study. Histochem Cell Biol 129(4):489–501
105. Nakae Y et al (2012) Quantitative evaluation of the beneficial effects in the mdx mouse of epigallocatechin gallate, an antioxidant polyphenol from green tea. Histochem Cell Biol 137(6):811–827
106. Nakamura A, Takeda S (2011) Mammalian models of duchenne muscular Dystrophy: pathological characteristics and therapeutic applications. J Biomed Biotechnol 2011:184393
107. Nicholson LV et al (1993) Functional significance of dystrophin positive fibres in duchenne muscular dystrophy. Arch Dis Child 68(5):632–636
108. Nigro G et al (1990) The incidence and evolution of cardiomyopathy in duchenne muscular dystrophy. Int J Cardiol 26(3):271–277
109. Olivier MD et al (2006) Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy. Am J Physiol Cell Physiol 290(2):C616–C625
110. Pan Y et al (2008) Curcumin alleviates dystrophic muscle pathology in mdx mice. Mol Cells 25(4):531–537
111. Pastoret C, Sebille A (1995) Mdx mice show progressive weakness and muscle deterioration with age. J Neurol Sci 129(2):97–105
112. Payne ET et al (2006) Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Muscle Nerve 33(1):66–77
113. Petrof B et al (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 90(8):3710–3714
114. Pierno S et al (2007) Role of tumour necrosis factor alpha, but not of cyclo-oxygenase-2-derived eicosanoids, on functional and morphological indices of dystrophic progression in mdx mice: a pharmacological approach. Neuropathol Appl Neurobiol 33(3):344–359
115. Porter JD et al (2002) A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum Mol Genet 11(3):263–272
116. Radley HG, Davies MJ, Grounds MD (2008) Reduced muscle necrosis and long-term benefits in dystrophic mdx mice after cV1q (blockade of TNF) treatment. Neuromuscul Disord 18(3):227–238
117. Rando TA (2001) The dystrophin–glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies. Muscle Nerve 24(112):1575–1594
118. Reutenauer J et al (2008) Investigation of Debio 025, a cyclophilin inhibitor, in the dystrophic mdx mouse, a model for duchenne muscular dystrophy. Br J Pharmacol 155(4):574–584
119. Romfh A, McNally EM (2010) Cardiac assessment in duchenne and becker muscular dystrophies. Curr Heart Fail Rep 7(4):212–218
120. Rybakova IN et al (2006) Dystrophin and utrophin bind actin through distinct modes of contact. J Biol Chem 281(15):9996–10001
121. Sabharwal R (2014) The link between stress disorders and autonomic dysfunction in muscular dystrophy. Front Physiol 5:25
122. Sali A et al (2012) Glucocorticoid-treated mice are an inappropriate positive control for long-term preclinical studies in the mdx mouse. PLoS ONE 7(4):e34204
123. Schara U, Mortier W (2001) Long-term steroid therapy in Duchenne muscular dystrophy-positive results versus side effects. J Clin Neuromuscu 2:179–183
124. Schreiber A et al (1987) Magnetic resonance imaging of children with Duchenne muscular dystrophy. Pediatr Radiol 17:495–497
125. Sekiguchi M et al (2009) A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice. Brain 132(Pt 1):124–135
126. Siegel AL et al (2009) Treatment with inhibitors of the NF-kappaB pathway improves whole body tension development in the mdx mouse. Neuromuscul Disord 19(2):131–139
127. Simonds AK et al (1998) Impact of nasal ventilation on survival in hypercapnic duchenne muscular dystrophy. Thorax 53(11):949–952
128. Smythe GM, White JD (2011) Voluntary wheel running in dystrophin-deficient (mdx) mice: relationships between exercise parameters and exacerbation of the dystrophic phenotype. PLoS Curr, 3, p. RRN1295
129. Spencer MJ, Croal IDE, Tidball JG (1995) Calpains are activated in necrotic fibers from mdx dystrophic mice. J Biol Chem 270(18):10909–10914
130. Spurney CF et al (2009) Dystrophin deficient cardiomyopathy in mouse: expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart. Neuromuscul Disord 18(5):371–381
131. Spurney CF et al (2012) CINRG pilot trial of coenzyme Q10 in steroid treated duchenne muscuar dystophy. Muscle Nerve 44(2):174–178
132. Stedman HH et al (1991) The mdx mouse diaphragm reproduces the degenerative changes of duchenne muscular dystrophy. Nature 352(6335):536–539
133. Stevens ED, Faulkner JA (2000) The capacity of mdx mouse diaphragm muscle to do oscillatory work. J Physiol 522(3):457–466
134. Stuckey DJ et al (2012) In vivo MRI characterization of progressive cardiac dysfunction in the mdx mouse model of muscular dystrophy. PLoS ONE 7(1):e28569
135. Tameyasu T, Ogura S, Ogihara K (2004) The effect of e-, i-, and n-nitric oxide synthase inhibition on colonic motility in normal and muscular dystrophy (Mdx) mice. Jpn J Physiol 54(6):555–566
136. Thanh LT et al (1995) Characterization of revertant muscle fibers in Duchenne muscular dystrophy, using exon-specific monoclonal antibodies against dystrophin. Am J Hum Genet 56(3):725–731
137. Tinsley J et al (1998) Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med 4(12):1441–1444
138. Tinsley J et al (2014) Future clinical and biomarker development for SMT C1100, the first utrophin modulator to enter clinical trials for duchenne muscular dystrophy (DMD). Neurology (8)82:10
139. Torelli S et al (1999) Expression, regulation and localisation of dystrophin isoforms in human foetal skeletal and cardiac muscle. Neuromuscul Disord 9(8):541–551
140. Turgeman T et al (2008) Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone. Neuromuscul Disord 18(11):857–868
141. Turner P et al (1993) Proteolysis results in altered leak channel kinetics and elevated free calcium in mdx muscle. J Membr Biol 133(3):243–251
142. Vaillend C, Ungerer A (1999) Behavioral characterization of mdx3cv mice deficient in C-terminal dystrophins. Neuromuscul Disord 9(5):296–304
143. Valentine B et al (1992) Canine X-linked muscular dystrophy as an animal model of Duchenne muscular dystrophy: a review. Am J Med Genet 42(3):352–356
144. Vallières L, Rivest S (1999) Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropin-releasing factor during endotoxemia. Endocrinology 140(9):3890–3903
145. Van Deutekom JC et al (2007) Local dystrophin restoration with antisense oligonucleotide PRO051. New Engl J Med 357(26):2677–2686
146. Van Erp C, Irwin NG, Hoey AJ (2006) Long-term administration of pirfenidone improves cardiac function in mdx mice. Muscle Nerve 34(3):327–334
147. Vandebrouck C et al (2002) Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. J Cell Biol 158(6):1089–1096
148. Venihaki M et al (2001) Corticotropin-releasing hormone regulates IL-6 expression during inflammation. J Clin Investig 108(8):1159–1166
149. Verhaart IEC, Aartsma-Rus A (2012) Gene therapy for duchenne muscular dystrophy. Curr Opin Neurol 25(5):588–596
150. Vilquin JT et al (1998) Evidence of mdx mouse skeletal muscle fragility in vivo by eccentric running exercise. Muscle Nerve 21(5):567–576
151. Viollet L et al (2012) Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in duchenne muscular dystrophy. Am J Cardiol 110(1):98–102
152. Wagner KR (2008) Approaching a new age in Duchenne muscular dystrophy treatment. Neurotherapeutics 5(4):583–591
153. Wehling-Henricks M, Lee JJ, Tidball JG (2004) Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophin-deficient skeletal muscle. Neuromuscul Disord 14(8–9):483–490
154. Wissing ER et al (2011) Debio-025 is more effective than prednisone in reducing muscular pathology in mdx mice. Neuromuscul Disord 20(11):753–760
155. Wu B et al (2010) Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino. Gene Ther 17(1):132-140
156. Yiu E, Kornberg A (2008) Duchenne muscular dystrophy. Neurol India 56(3):236–247
157. Yokota T et al (2006) Expansion of revertant fibers in dystrophic mdx muscles reflects activity of muscle precursor cells and serves as an index of muscle regeneration. J Cell Sci 119(Pt 13):2679–2687
158. Yokota T et al (2009) Efficacy of systemic morpholino exon–skipping in duchenne dystrophy dogs 65(6):667–676
159. Yokota T et al (2012) Exon skipping for nonsense mutations in Duchenne muscular dystrophy: too many mutations, too few patients?. Expert Opin Biol Ther 12(9):1141–1152.
160. Yoshida M et al (2006) Dietary NaCl supplementation prevents muscle necrosis in a mouse model of duchenne muscular dystrophy. Am J Physiol Regul Intregr Comp Physiol 1(290):449–455
161. Zeiger U, Mitchell CH, Khurana TS (2010) Superior calcium homeostasis of extraocular muscles. Exp Eye Res 91(5):613–622