Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

Human Molecular Genetics

Volumn 24, Issue 21, 2015, Pages 6041-6053

  Pelosi, Laura ^a   Berardinelli, Maria Grazia ^a   Forcina, Laura ^a   Spelta, Elisa ^a   Rizzuto, Emanuele ^b   Nicoletti, Carmine ^a   Camilli, Carlotta ^a   Testa, Erika ^a   Catizone, Angela ^b   De Benedetti, Fabrizio ^c   Musarò, Antonio ^a,d  

^a Pasteur Institute   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^d ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 1BETA; INTERLEUKIN 6; TUMOR NECROSIS FACTOR ALPHA; INTERLEUKIN-6, MOUSE; NF-KAPPA B KINASE; PROTEIN SERINE THREONINE KINASE;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DIAPHRAGM; DISEASE COURSE; DISEASE PREDISPOSITION; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; MOUSE; MUSCLE ATROPHY; MUSCLE MASS; MUSCLE NECROSIS; MUSCLE REGENERATION; MUSCLE STEM CELL; MUSCULAR DYSTROPHY; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SKELETAL MUSCLE SATELLITE CELL; WILD TYPE; X CHROMOSOME LINKED MUSCULAR DYSTROPHIC MOUSE; ANIMAL; DUCHENNE MUSCULAR DYSTROPHY; GENETICS; METABOLISM; MUSCLE DEVELOPMENT; PATHOLOGY; SKELETAL MUSCLE; STEM CELL;

ANIMALS; DOWN-REGULATION; INTERLEUKIN-6; MICE; MICE, INBRED MDX; MUSCLE DEVELOPMENT; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, DUCHENNE; PHENOTYPE; PROTEIN-SERINE-THREONINE KINASES; SATELLITE CELLS, SKELETAL MUSCLE; STEM CELLS;

EID: 84949257257     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv323     Document Type: Article

References (85)

1. Deconinck, N., Dan, B. (2007) Pathophysiology of duchenne muscular dystrophy: current hypotheses. Pediatr. Neurol., 36, 1-7.
2. Carnwath, J.W., Shotton, D.M. (1987) Muscular dystrophy in the mdx mouse: histopathology of the soleus and extensor digitorum longus muscles. J. Neurol. Sci., 80, 39-54.
3. Grounds, M.D., Radley, H.G., Lynch, G.S., Nagaraju, K., De Luca, A. (2008) Towards developing standard operating procedures for pre-clinical testing in the mdx mouse model of Duchenne muscular dystrophy. Neurobiol. Dis., 31, 1-19.
4. Grounds, M.D. (2008) Two-tiered hypotheses for Duchenne muscular dystrophy. Cell Mol. Life Sci., 65, 1621-1625.
5. Grounds, M.D., Shavlakadze, T. (2011) Growing muscle has different sarcolemmal properties from adult muscle: a proposal with scientific and clinical implications: reasons to reassess skeletal muscle molecular dynamics, cellular responses and suitability of experimental models of muscle disorders. Bioessays, 33, 458-468.
6. Turk, R., Sterrenburg, E., de Meijer, E.J., van Ommen, G.J., den Dunnen, J.T., 't Hoen, P.A. (2005) Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling. BMC. Genomics, 6, 98.
7. Willmann, R., De Luca, A., Benatar, M., Grounds, M., Dubach, J., Raymackers, J.M., Nagaraju, K. (2012) Enhancing translation: Guidelines for standard pre-clinical experiments in mdx mice. Neuromuscul. Disord., 22, 43-49.
8. Pescatori, M., Broccolini, A., Minetti, C., Bertini, E., Bruno, C., D'amico, A., Bernardini, C., Mirabella, M., Silvestri, G., Giglio, V., et al. (2007) Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression. FASEB J, 21, 1210-1226.
9. Porter, J.D., Khanna, S., Kaminski, H.J., Rao, J.S., Merriam, A.P., Richmonds, C.R., Leahy, P., Li, J., Guo, W., Andrade, F.H. (2002) A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum. Mol. Genet., 11, 263-272.
10. Evans, N.P., Misyak, S.A., Robertson, J.L., Bassaganya-Riera, J., Grange, R.W. (2009) Immune-mediated mechanisms potentially regulate the disease time-course of duchenne muscular dystrophy and provide targets for therapeutic intervention. PM. R., 1, 755-768.
11. Messina, S., Vita, G.L., Aguennouz, M., Sframeli, M., Romeo, S., Rodolico, C., Vita, G. (2011) Activation of NF-kappaB pathway in Duchenne muscular dystrophy: relation to age. Acta Myol., 30, 16-23.
12. Rufo, A., Del, F.A., Capulli, M., Carvello, F., De, P.L., Ferrari, S., Pierroz, D., Morandi, L., De, S.M., Rucci, N., et al. (2011) Mechanisms inducing low bone density in Duchenne muscular dystrophy in mice and humans. J. Bone Miner. Res., 26, 1891-1903.
13. Goodman, M.N. (1994) Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc. Soc. Exp. Biol. Med, 205, 182-185.
14. Haddad, F., Zaldivar, F., Cooper, D.M., Adams, G.R. (2005) IL-6-induced skeletal muscle atrophy. J Appl. Physiol. (1985.), 98, 911-917.
15. Tsujinaka, T., Ebisui, C., Fujita, J., Kishibuchi, M., Morimoto, T., Ogawa, A., Katsume, A., Ohsugi, Y., Kominami, E., Monden, M. (1995) Muscle undergoes atrophy in association with increase of lysosomal cathepsin activity in interleukin-6 transgenic mouse. Biochem. Biophys. Res. Commun., 207, 168-174.
16. Huynh, T., Uaesoontrachoon, K., Quinn, J.L., Tatem, K.S., Heier, C.R., Van der Meulen, J.H., Yu, Q., Harris, M., Nolan, C. J., Haegeman, G., et al. (2013) Selective modulation through the glucocorticoid receptor ameliorates muscle pathology in mdx mice. J. Pathol., 231, 223-235.
17. Pelosi, L., Berardinelli, M.G., De, P.L., Nicoletti, C., D'amico, A., Carvello, F., Moneta, G.M., Catizone, A., Bertini, E., De, B.F., et al. (2015) Functional and morphological improvement of dystrophic muscle by interleukin 6 receptor blockade. EBio-Medicine., 2, 285-293.
18. Price, F.D., von Maltzahn, J., Bentzinger, C.F., Dumont, N.A., Yin, H., Chang, N.C., Wilson, D.H., Frenette, J., Rudnicki, M.A. (2014) Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat. Med., 20, 1174-1181.
19. Tierney, M.T., Aydogdu, T., Sala, D., Malecova, B., Gatto, S., Puri, P.L., Latella, L., Sacco, A. (2014) STAT3 signaling controls satellite cell expansion and skeletal muscle repair. Nat. Med, 20, 1182-1186.
20. Carson, J.A., Baltgalvis, K.A. (2010) Interleukin 6 as a key regulator of muscle mass during cachexia. Exerc. Sport Sci. Rev., 38, 168-176.
21. Rose-John, S. (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int. J. Biol. Sci., 8, 1237-1247.
22. Mihara, M., Hashizume, M., Yoshida, H., Suzuki, M., Shiina, M. (2012) IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin. Sci. (Lond), 122, 143-159.
23. Gabay, C. (2006) Interleukin-6 and chronic inflammation. Arthritis Res. Ther., 8 Suppl 2, S3.
24. Iwase, S., Murakami, T., Saito, Y., Nakagawa, K. (2004) Steep elevation of blood interleukin-6 (IL-6) associated only with late stages of cachexia in cancer patients. Eur. Cytokine Netw., 15, 312-316.
25. Scott, H.R., McMillan, D.C., Crilly, A., McArdle, C.S., Milroy, R. (1996) The relationship between weight loss and interleukin 6 in non-small-cell lung cancer. Br. J. Cancer, 73, 1560-1562.
26. Gomez, C.R., Karavitis, J., Palmer, J.L., Faunce, D.E., Ramirez, L., Nomellini, V., Kovacs, E.J. (2010) Interleukin-6 contributes to age-related alteration of cytokine production by macrophages. Mediators. Inflamm., 2010, 475139.
27. Kurek, J.B., Nouri, S., Kannourakis, G., Murphy, M., Austin, L. (1996) Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscle. Muscle Nerve, 19, 1291-1301.
28. Pedersen, B.K., Febbraio, M.A. (2008) Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev., 88, 1379-1406.
29. Serrano, A.L., Baeza-Raja, B., Perdiguero, E., Jardi, M., Munoz-Canoves, P. (2008) Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab., 7, 33-44.
30. Pelosi, M., De Rossi, M., Barberi, L., Musaro, A. (2014) IL-6 impairs myogenic differentiation by downmodulation of p90RSK/eEF2 and mTOR/p70S6K axes, without affecting AKT activity. Biomed. Res. Int., 2014, 206026.
31. Manning, J., Kulbida, R., Rai, P., Jensen, L., Bouma, J., Singh, S. P., O'Malley, D., Yilmazer-Hanke, D. (2014) Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy. Exp. Physiol., 99, 1370-1386.
32. Fuster, J.J., Walsh, K. (2014) The good, the bad, and the ugly of interleukin-6 signaling. EMBO J., 33, 1425-1427.
33. Munoz-Canoves, P., Scheele, C., Pedersen, B.K., Serrano, A.L. (2013) Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS J., 280, 4131-4148.
34. De Benedetti, F., Alonzi, T., Moretta, A., Lazzaro, D., Costa, P., Poli, V., Martini, A., Ciliberto, G., Fattori, E. (1997) Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J. Clin. Invest., 99, 643-650.
35. Coulton, G.R., Curtin, N.A., Morgan, J.E., Partridge, T.A. (1988) The mdx mouse skeletal muscle myopathy: II. Contractile properties. Neuropathol. Appl. Neurobiol., 14, 299-314.
36. Pastoret, C., Sebille, A. (1995) Age-related differences in regeneration of dystrophic (mdx) and normal muscle in the mouse. Muscle Nerve, 18, 1147-1154.
37. Moghadaszadeh, B., Albrechtsen, R., Guo, L.T., Zaik, M., Kawaguchi, N., Borup, R.H., Kronqvist, P., Schroder, H.D., Davies, K. E., Voit, T., et al. (2003) Compensation for dystrophin-deficiency: ADAM12 overexpression in skeletal muscle results in increased alpha 7 integrin, utrophin and associated glycoproteins. Hum. Mol. Genet., 12, 2467-2479.
38. Nowak, K.J., Davies, K.E. (2004) Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for treatment. EMBO Rep., 5, 872-876.
39. Carosio, S., Berardinelli, M.G., Aucello, M., Musaro, A. (2011) Impact of ageing on muscle cell regeneration. Ageing Res. Rev., 10, 35-42.
40. Cannon, J.G., St Pierre, B.A. (1998) Cytokines in exertioninduced skeletalmuscle injury. Mol. Cell Biochem., 179, 159-167.
41. Tidball, J.G. (1995) Inflammatory cell response to acute muscle injury. Med. Sci. Sports Exerc., 27, 1022-1032.
42. Croker, B.A., Krebs, D.L., Zhang, J.G., Wormald, S., Willson, T. A., Stanley, E.G., Robb, L., Greenhalgh, C.J., Forster, I., Clausen, B.E., et al. (2003) SOCS3 negatively regulates IL-6 signaling in vivo. Nat. Immunol., 4, 540-545.
43. Lang, R., Pauleau, A.L., Parganas, E., Takahashi, Y., Mages, J., Ihle, J.N., Rutschman, R., Murray, P.J. (2003) SOCS3 regulates the plasticity of gp130 signaling. Nat. Immunol., 4, 546-550.
44. McDonald, A.A., Hebert, S.L., Kunz, M.D., Ralles, S.J., McLoon, L.K. (2015) Disease course in mdx:utrophin+/-mice: comparison of three mouse models of Duchenne muscular dystrophy. Physiol Rep., 3, e12391.
45. Matsuda, R., Nishikawa, A., Tanaka, H. (1995) Visualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophindeficient muscle. J. Biochem., 118, 959-964.
46. Zatz, M., Rapaport, D., Vainzof, M., Passos-Bueno, M.R., Bortolini, E.R., Pavanello, R.C., Peres, C.A. (1991) Serum creatine-kinase (CK) and pyruvate-kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy. J. Neurol. Sci., 102, 190-196.
47. Burdi, R., Didonna, M.P., Pignol, B., Nico, B., Mangieri, D., Rolland, J.F., Camerino, C., Zallone, A., Ferro, P., Andreetta, F., et al. (2006) First evaluation of the potential effectiveness in muscular dystrophy of a novel chimeric compound, BN 82270, acting as calpain-inhibitor and anti-oxidant. Neuromuscul. Disord., 16, 237-248.
48. De Luca, A., Pierno, S., Liantonio, A., Cetrone, M., Camerino, C., Fraysse, B., Mirabella, M., Servidei, S., Ruegg, U.T., Conte, C.D. (2003) Enhanced dystrophic progression in mdx mice by exercise and beneficial effects of taurine and insulin-like growth factor-1. J. Pharmacol. Exp. Ther., 304, 453-463.
49. Granchelli, J.A., Pollina, C., Hudecki, M.S. (2000) Pre-clinical screening of drugs using the mdx mouse. Neuromuscul. Disord., 10, 235-239.
50. Nakamura, J., Tajima, G., Sato, C. (2003) ATP regulation of calcium binding in Ca2+-ATPase molecules of the sarcoplasmic reticulum. Ann. N. Y. Acad. Sci., 986, 341-343.
51. Vilquin, J.T., Brussee, V., Asselin, I., Kinoshita, I., Gingras, M., Tremblay, J.P. (1998) Evidence of mdx mouse skeletal muscle fragility in vivo by eccentric running exercise. Muscle Nerve, 21, 567-576.
52. Carlson, C.G., 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, 719-730.
53. Messina, S., Bitto, A., Aguennouz, M., Minutoli, L., Monici, M. C., Altavilla, D., Squadrito, F., Vita, G. (2006) Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice. Exp. Neurol., 198, 234-241.
54. Monici, M.C., Aguennouz, M., Mazzeo, A., Messina, C., Vita, G. (2003) Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne muscular dystrophy. Neurology, 60, 993-997.
55. Cai, D., Frantz, J.D., Tawa, N.E. Jr, Melendez, P.A., Oh, B.C., Lidov, H.G., Hasselgren, P.O., Frontera, W.R., Lee, J., Glass, D. J., et al. (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, 119, 285-298.
56. Guttridge, D.C., Mayo, M.W., Madrid, L.V., Wang, C.Y., Baldwin, A.S. Jr (2000) NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science, 289, 2363-2366.
57. Sriram, S., Subramanian, S., Sathiakumar, D., Venkatesh, R., Salerno, M.S., McFarlane, C.D., Kambadur, R., Sharma, M. (2011) Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-kappaB. Aging Cell, 10, 931-948.
58. Nathan, C. (2002) Points of control in inflammation. Nature, 420, 846-852.
59. Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R.K., Chazaud, B. (2007) Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med., 204, 1057-1069.
60. Seale, P., Sabourin, L.A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., Rudnicki, M.A. (2000) Pax7 is required for the specification of myogenic satellite cells. Cell, 102, 777-786.
61. Zammit, P.S. (2008) Skeletal Muscle Repair and Regeneration. Springer Press, Dordrecht, NL.
62. Creuzet, S., Lescaudron, L., Li, Z., Fontaine-Perus, J. (1998) MyoD, myogenin, and desmin-nls-lacZ transgene emphasize the distinct patterns of satellite cell activation in growth and regeneration. Exp. Cell Res., 243, 241-253.
63. Rantanen, J., Hurme, T., Lukka, R., Heino, J., Kalimo, H. (1995) Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells. Lab. Invest., 72, 341-347.
64. Kurosaka, M., Machida, S. (2013) Interleukin-6-induced satellite cell proliferation is regulated by induction of the JAK2/STAT3 signalling pathway through cyclin D1 targeting. Cell Prolif., 46, 365-373.
65. Sacco, A., Doyonnas, R., Kraft, P., Vitorovic, S., Blau, H.M. (2008) Self-renewal and expansion of single transplanted muscle stem cells. Nature, 456, 502-506.
66. Joe, A.W., Yi, L., Natarajan, A., Le Grand, F., So, L., Wang, J., Rudnicki, M.A., Rossi, F.M. (2010) Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat. Cell Biol., 12, 153-163.
67. Mozzetta, C., Consalvi, S., Saccone, V., Tierney, M., Diamantini, A., Mitchell, K.J., Marazzi, G., Borsellino, G., Battistini, L., Sassoon, D., et al. (2013) Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice. EMBO Mol. Med., 5, 626-639.
68. Uezumi, A., Fukada, S., Yamamoto, N., Takeda, S., Tsuchida, K. (2010) Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol., 12, 143-152.
69. Uezumi, A., Ito, T., Morikawa, D., Shimizu, N., Yoneda, T., Segawa, M., Yamaguchi, M., Ogawa, R., Matev, M.M., Miyagoe-Suzuki, Y., et al. (2011) Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J. Cell Sci., 124, 3654-3664.
70. Hidestrand, M., Richards-Malcolm, S., Gurley, C.M., Nolen, G., Grimes, B., Waterstrat, A., Zant, G.V., Peterson, C.A. (2008) Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletalmuscle. J. Gerontol. ABiol. Sci. Med. Sci., 63, 566-579.
71. Mitchell, P.O., Mills, T., O'Connor, R.S., Kline, E.R., Graubert, T., Dzierzak, E., Pavlath, G.K. (2005) Sca-1 negatively regulates proliferation and differentiation of muscle cells. Dev. Biol., 283, 240-252.
72. Willmann, R., Possekel, S., Dubach-Powell, J., Meier, T., Ruegg, M.A. (2009) Mammalian animal models for Duchenne muscular dystrophy. Neuromuscul. Disord., 19, 241-249.
73. Turk, R., Sterrenburg, E., van derWees, C.G., de Meijer, E.J., de Menezes, R.X., Groh, S., Campbell, K.P., Noguchi, S., van Ommen, G.J., den Dunnen, J.T., et al. (2006) Common pathological mechanisms in mouse models for muscular dystrophies. FASEB J., 20, 127-129.
74. Acharyya, S., Villalta, S.A., Bakkar, N., Bupha-Intr, T., Janssen, P.M., Carathers, M., Li, Z.W., Beg, A.A., Ghosh, S., Sahenk, Z., et al. (2007) Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J. Clin. Invest., 117, 889-901.
75. Mourkioti, F., Rosenthal, N. (2008) NF-kappaB signaling in skeletal muscle: prospects for intervention in muscle diseases. J. Mol. Med. (Berl), 86, 747-759.
76. Brack, A.S., Rando, T.A. (2012) Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Cell Stem Cell, 10, 504-514.
77. Peault, B., Rudnicki, M., Torrente, Y., Cossu, G., Tremblay, J.P., Partridge, T., Gussoni, E., Kunkel, L.M., Huard, J. (2007) Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Mol. Ther., 15, 867-877.
78. Penton, C.M., Thomas-Ahner, J.M., Johnson, E.K., McAllister, C., Montanaro, F. (2013) Muscle side population cells from dystrophic or injured muscle adopt a fibro-adipogenic fate. PLoS. One., 8, e54553.
79. Kelly, M., Keller, C., Avilucea, P.R., Keller, P., Luo, Z., Xiang, X., Giralt, M., Hidalgo, J., Saha, A.K., Pedersen, B.K., et al. (2004) AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem. Biophys. Res. Commun., 320, 449-454.
80. Keller, C., Steensberg, A., Pilegaard, H., Osada, T., Saltin, B., Pedersen, B.K., Neufer, P.D. (2001) Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J., 15, 2748-2750.
81. Musaro, A. (2014) The basis of muscle regeneration. Adv. Biol., 2014, 1-16.
82. Del Prete, Z., Musaro, A., Rizzuto, E. (2008) Measuring mechanical properties, including isotonic fatigue, of fast and slow MLC/mIgf-1 transgenic skeletal muscle. Ann. Biomed. Eng., 36, 1281-1290.
83. Messina, S., Bitto, A., Aguennouz, M., Mazzeo, A., Migliorato, A., Polito, F., Irrera, N., Altavilla, D., Vita, G.L., Russo, M., et al. (2009) Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone. Exp. Neurol., 220, 349-358.
84. Conner, J.D., Wolden-Hanson, T., Quinn, L.S. (2014) Assessment of murine exercise endurance without the use of a shock grid: an alternative to forced exercise. J. Vis. Exp., 90, e51846.
85. Hamer, P.W., McGeachie, J.M., Davies, M.J., Grounds, M.D. (2002) Evans Blue Dye as an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability. J. Anat., 200, 69-79.