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Animal Models for Muscle Disease and Muscle Gene Therapy

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Abstract

It is currently estimated that roughly 50,000 Americans are affected by some form of muscular dystrophy and many others by the various forms of myopathies. Animal models are critical for our understanding of the numerous muscular diseases that affect people and for the development of targeted gene therapeutics to treat such diseases. Our current understanding of the pathophysiology of these diseases would not be possible without the aid of animal modeling. Multiple animal models have been described, including mice, cats, dogs pigs, etc.; however, the discussion in this chapter will primarily focus on mice and dogs because these two animal models have been more rigorously researched and described. The overall objectives of this chapter are to review the available animal models and their limitations, disease-specific mutations, clinical disease manifestations, and recent advances in associated therapeutic modalities for various muscular disorders, with a focus on dystrophinopathies and limb-girdle muscular dystrophies.

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References

  1. Chinwalla A, Cook L, Delehaunty K, Fewell G, Fulton L, Fulton R, Graves T, Hillier L, Mardis E, McPherson J, Miner T, Nash W, Nelson J, Nhan M, Pepin K, Phol C, Ponce T, Schultz B, Thompson J, Travaskis E, Waterston R, Wendl M, Wilson R, Yang S, An P, Berry E, Birren B, Bloom T, Brown D, Butler J, Daly M, David R, Deri J, Dodge S, Foley K, Gage D, Gnerre S, Holzer T, Jaffe D, Kamal M, Karlsson E, Kells C, Kirby A, Kulbokas E, Lander E, Landers T, Leger J, Levine R, Lindblad-Toh K, Mauceli E, Mayer J, McCarthy M, Meldrim J, Mesirov J, Nicol R, Nusbaum C, Seaman S, Sharpe T, Sheridan A, Singer J, Santos R, Spencer B, Stange-Thomann N, Vinson J, Wade C, Wierzbowski J, Wyman D, Zody M, Birney E, Goldman N, Kasprzyk A, Mongin E, Rust A, Slater G, Stabenau A, Ureta-Vidal A, Whelan S, Ainscough R, Attwood J, Bailey J, Barlow K, Beck S, Burton J, Butler J, Campbell R, Carninci P, Cawley S, Chiaromonte F, Chinwalla A, Church D, Clamp M, Clee C, Collins F, Cook L, Copley R, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty K, Deri J, Dermitzakis E, Dewey C, Dickens N et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420(6915):520–562. http://www.nature.com/nature/journal/v420/n6915/suppinfo/nature01262_S1.html

  2. Monaco A, Neve R, Colletti-Feener C, Bertelson C, Kurnit D, Kunkel L (1986) Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 33:646–650. https://doi.org/10.1038/323646a0

    Article  Google Scholar 

  3. Hoffman E, Brown R, Kunkel L (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51(6):919–928

    Article  CAS  PubMed  Google Scholar 

  4. Spurney C, Knoblach S, Pistilli E, Nagaraju K, Martin G, Hoffman E (2008) Dystrophin-deficient cardiomyopathy in mouse: expression of Nox4 and Lox are associated with fibrosis and altered functional parameter in the heart. Neuromuscul Disord 18(5):371–381

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fine D, Shin J, Yue Y, Volkmann D, Leach S, Smith B, McIntosh M, Duan D (2011) Age-matched comparison reveals early electrocardiography and echocardiography changes in dystrophin-deficient dogs. Neuromuscul Disord 21(7):453–461. https://doi.org/10.1016/j.nmd.2011.03.010

    Article  PubMed  PubMed Central  Google Scholar 

  6. Beggs A (1997) Dystrophinopathy, the expanding phenotype dystrophin abnormalities in X-linked dilated cardiomyopathy. Circulation 95(10):2344–2347

    Article  CAS  PubMed  Google Scholar 

  7. Bouhouch R, Elhouari T, Oukerraj L, Fellat I, Zarzur J, Bennani R, Arharbi M (2008) Management of cardiac involvement in neuromuscular diseases: review. Open Cariovasc Med J 2:93–96. https://doi.org/10.2174/1874192400802010093

    Article  Google Scholar 

  8. Verhaert D, Richards K, Rafael-Fortney J, Raman S (2011) Cardiac involvement in patients with muscular dystrophies: magnetic resonance imaging phenotype and genotypic considerations. Circ Cardiovasc Imaging 4(1):67–76

    Article  PubMed  PubMed Central  Google Scholar 

  9. Carpenter J, Hoffman E, Romanul F, Kunkel L, Rosales R, Ma N, Dasbach J, Rae J, Moore F, McAfee M, Pearce L (1989) Feline muscular dystrophy with dystrophin deficiency. Am J Pathol 135(5):909–919

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Klymiuk N, Blutke A, Graf A, Krause S, Burkhardt K, Wuensch A, Krebs S, Kessler B, Zakhartchenko V, Kurome M, Kemter E, Hagashima H, Schoser B, Herbach N, Blum H, Wanke R, Aartsma-Rus A, Thirion C, Lochmuller H, Walter M, Wolf E (2013) Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle. Hum Mol Genet 22(21):4368–4382. https://doi.org/10.1093/hmg/ddt287

    Article  CAS  PubMed  Google Scholar 

  11. Collins C, Morgan J (2003) Duchenne’s muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies. Int J Exp Pathol 84(4):165–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sicinski P, Geng Y, Ryder-Cook A, Barnard E, Darlison M, Barnard P (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244(4912):1578–1580

    Article  CAS  PubMed  Google Scholar 

  13. Lefaucheur J, Pastoret C, Sebille A (1995) Phenotype of dystrophinopathy in old mdx mice. Anat Rec 242(1):70–76

    Article  CAS  PubMed  Google Scholar 

  14. Sandri M, Podhorska-Okolow M, Geromel V, Rizzi C, Arslan P, Franceschi C, Carraro U (1997) Exercise Induces Myonuclear Ubiquitination and Apoptosis in Dystrophin-deficient Muscle of Mice. J Neuropathol Exp Neurol 56(1):45–57. https://doi.org/10.1097/00005072-199701000–00005

    Article  CAS  PubMed  Google Scholar 

  15. Bostick B, Yue Y, Long C, Duan D (2008) Prevention of dystrophin-deficient cardiomyopathy in twenty-one-month-old carrier mice by mosaic dystrophin expression or complementary dystrophin/utrophin expression. Circ Res 102(1):121–130. https://doi.org/10.1161/CIRCRESAHA.107.162982

    Article  CAS  PubMed  Google Scholar 

  16. Stedman H, Sweeney H, Shrager J, Maquire H, Panettieri R, Petrof B, Narusawa M, Leferovich J, Sladky J, Kelly A (1991) The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352(6335):536–539

    Article  CAS  PubMed  Google Scholar 

  17. Metzger T, Gache V, Xu M, Cadot B, Folker E, Richardson B, Gomes E, Baylies M (2012) MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature 484(7392):120–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Duddy W, Duguez S, Johnston H, Cohen T, Phadke A, Gordish-Dressman H, Nagaraju K, Gnocchi V, Low S, Partridge T (2016) Muscular dystrophy in the mdx mouse is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia. Skelet Muscle 5:16. https://doi.org/10.1186/s13395-015-0041-y

    Article  CAS  Google Scholar 

  19. Danko I, Chapman V, Wolff J (1992) The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. Pediatr Res 32(1):128–131. https://doi.org/10.1203/00006450-199207000-00025

    Article  CAS  PubMed  Google Scholar 

  20. Blake D, Tinsley J, Davies K (1996) Utrophin: a structural and functional comparison to dystrophin. Brain Pathol 6(1):37–47

    Article  CAS  PubMed  Google Scholar 

  21. Deconinck A, Rafael J, Skinner J, Brown S, Potter A, Metzinger L, Watt D, Dickson J, Tinsley J, Davies K (1997) Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 90(4):717–727

    Article  CAS  PubMed  Google Scholar 

  22. Isaac C, Wright A, Usas A, Li H, Tang Y, Mu X, Greco N, Dong Q, Vo N, Kang J, Wang B, Huard J (2013) Dystrophin and utrophin “double knockout” dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities. J Orthop Res 31(3):33–349. https://doi.org/10.1002/jor.22236

    Article  Google Scholar 

  23. Fukada S, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, Ito T, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H (2010) Genetic background affects properties of satellite cells and mdx phenotypes. Am J Pathol 176(5):2414–2424. https://doi.org/10.2353/ajpath.2010.090887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chapman V, Miller D, Armstrong D, Caskey C (1989) Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci U S A 86(4):1292–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cox G, Phelps S, Chapman V, Chamberlain J (1993) New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nat Genet 4(1):87–93. https://doi.org/10.1038/ng0593-87

    Article  CAS  PubMed  Google Scholar 

  26. Kohn B, Guscetti F, Waxenberger M, Augsburger H (1993) Muscular dystrophy in a cat. Tierarztl Prax 21(5):451–457

    CAS  PubMed  Google Scholar 

  27. Blunden A, Gower S (2011) Hypertrophic feline muscular dystrophy: diagnostic overview and a novel immunohistochemical diagnostic method using formalin-fixed tissue. Vet Rec 168(19):510. https://doi.org/10.1136/vr.d1119

    Article  CAS  PubMed  Google Scholar 

  28. Gaschen L, Lang J, Lin S, Ade-Damilano M, Busato A, Lombard C, Gaschen F (1999) Cardiomyopathy in dystrophin-deficient hypertrophic feline muscular dystrophy. J Vet Intern Med 13(4):346–356

    Article  CAS  PubMed  Google Scholar 

  29. Sharp N, Kornegay J, Camp SV, Herbstreith M, Secore S, Kettle S, Hung W, Constatinou C, Dykstra M, Roses A, Bartlett R (1992) An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics 13(1):115–121

    Article  CAS  PubMed  Google Scholar 

  30. Schatzberg S, Olby N, Breen M, Anderson L, Langford C, Dickens H, Wilton S, Zeiss C, Binns M, Kornegay J, Morris G, sharp N (1999) Molecular analysis of a spontaneous dystrophin “knockout” dog. Neuromuscul Disord 9(5):289–295

    Article  CAS  PubMed  Google Scholar 

  31. Winand N, Pradham D, Cooper B (1994) Molecular characterization of severe Duchenne-type muscular dystrophy in a family of Rottweiler dogs. In: Molecular mechanisms of neuromuscular disease. University of Arizona, Tuscon

    Google Scholar 

  32. Smith B, Kornegay J, Duan D (2007) Independent canine models of Duchenne muscular dystrophy due to intronic insertions of repetitive DNA. Mol Ther 15(Supplement 1):S51

    Google Scholar 

  33. Ito D, Kitagawa M, Jeffery N, Okada M, Yoshida M, Kobayashi M, Nakamura A, Watari T (2011) Dystrophin-deficient muscular dystrophy in an Alaskan malamute. Vet Rec 169(5):127. https://doi.org/10.1136/vr.d2693

    Article  CAS  PubMed  Google Scholar 

  34. Shrader SM, Jung S, Denney TS, Smith BF (2018) Characterization of Australian Labradoodle dystrophinopathy. Neuromuscular Disord 28(11):927–937. https://doi.org/10.1016/j.nmd.2018.08.008

    Article  Google Scholar 

  35. Wieczorek L, Garosi L, Shelton G (2006) Dystrophin-deficient muscular dystrophy in an old English sheepdog. Vet Rec 158:270–273

    Article  CAS  PubMed  Google Scholar 

  36. Beltran E, Shelton G, Guo L, Dennis R, Sanchez-Masian D, Robinson D, Risio LD (2015) Dystrophin-deficient muscular dystrophy in a Norfolk terrier. J Small Anim Pract 56(5):351–354. https://doi.org/10.1111/jsap.12292

    Article  CAS  PubMed  Google Scholar 

  37. Kornegay J, Bogan J, Bogan D, Childers M, Li J, Nghiem P, Detwiler D, Larsen C, Grange R, Bhavaraju-Sanka R, Tou S, Keene B, Howard J, Wang J, Fan Z, Schatzberg S, Styner M, Flanigan K, Xiao X, Hoffman E (2012) Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies. Mamm Genome 23(1-2):85–108. https://doi.org/10.1007/s00335-011-9382-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Atencia-Fernandez S, Shiel R, Mooney C, Nolan C (2015) Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes. Anim Genet 46(2):175–184. https://doi.org/10.1111/age.1226

    Article  CAS  PubMed  Google Scholar 

  39. Jones B, Brennan S, Mooney C, Callahan J, McAllister H, Guo L, Martin P, Engvall E, Shelton G (2004) Muscular dystrophy with truncated dystrophin in a family of Japanese Spitz dogs. J Neurol Sci 217(2):143–149

    Article  CAS  PubMed  Google Scholar 

  40. Walmsley G, Arechavala-Gomeza V, Fernandez-Fuente M, Burke M, Nagel N, Holder A, Stanley R, Chandler K, marks S, Muntoni F, Shelton G, Piercy R (2010) A Duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient Cavalier King Charles spaniels is amenable to exon 51 skipping. PLoS One 5(1):e8647. https://doi.org/10.1371/journal.pone.0008647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Valentine B, Cooper B, de Lahunta A, O’Quinn R, Blue J (1988) Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies. J Neurol Sci 88(1-3):69–81

    Article  CAS  PubMed  Google Scholar 

  42. Shimatsu Y, Katagiri K, Furuta T, Nakura M, Tanioka Y, Yuasa K, Tomohiro M, Kornegay J, Nonaka I, Takeda S (2003) Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp Anim 52(2):93–97

    Article  CAS  PubMed  Google Scholar 

  43. Smith B, Yue Y, Woods P, Kornegay J, Shin J, Williams R, Duan D (2011) An intronic LINE-1 element insertion in the dystrophin gene aborts dystrophin expression and results in Duchenne-like muscular dystrophy in the Corgi breed. Lab Investig 91(2):216–231

    Article  CAS  PubMed  Google Scholar 

  44. Schatzberg S, Anderson L, Wilton S, Kornegay J, Mann C, Solomon G, Sharp N (1998) Alternative dystrophin gene transcripts in golden retriever muscular dystrophy. Muscle Nerve 21(8):991–998

    Article  CAS  PubMed  Google Scholar 

  45. Howell J, Lochmuller H, O’Hara A, Fletcher S, Kakulas B, Massie B, Nalbantoglu J, Karpati G (1998) High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: prolongation of expression with immunosuppression. Hum Gene Ther 9(5):629–634. https://doi.org/10.1089/hum.1998.9.5-629

    Article  CAS  PubMed  Google Scholar 

  46. Nakagaki K, Gebhard D, Bogan D, Kornegay J (1994) Selection of canine myogenic cells with panning. Muscle Nerve 17(Supplement 1):S260

    Google Scholar 

  47. Nakagaki K, Gebhard D, Bogan D, Kornegay J (1994) A quantitative comparison of NCAM-positive muscle cells from normal and dystrophic dogs. Muscle Nerve 17(Supplement 1):S193

    Google Scholar 

  48. Tremblay J, Malouin F, Roy R, Huard J, Bouchard J, Satoh A, Richards C (1993) Results of a triple blind clinical study of myoblast transplantations without immunosuppressive treatment in young boys with Duchenne muscular dystrophy. Cell Transplant 2(2):99–112

    Article  CAS  PubMed  Google Scholar 

  49. Miller R, Sharma K, Pavlath G, Gussoni E, Mynhier M, Lanctot A, Greco C, Steinman L, Blau H (1997) Myoblast transplantation in Duchenne muscular dystrophy: The San Francisco Study. Muscle Nerve 20(4):469–478

    Article  CAS  PubMed  Google Scholar 

  50. Gussoni E, Blau H, Kunkel L (1997) The fate of individual myoblasts after transplantation into muscles of DMD patients. Nat Med 3:970–977. https://doi.org/10.1038/nm0997-970

    Article  CAS  PubMed  Google Scholar 

  51. Townsend D, Turner I, Yasuda S, Martindale J, Davis J, Shillingford M, Kornegay J, Metzger J (2010) Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. J Clin Invest 120(4):1140–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mahmood O, Jiang X (2014) Limb-girdle muscular dystrophies: where next after six decades from the first proposal. Mol Med Rep 9(5):1515–1532. https://doi.org/10.3892/mmr.2014.2048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Olive M, Goldfarb L, Shatunov A, Fischer D, Ferrer I (2005) Myotilinopathy: refining the clinical and myopathological phenotype. Brain 128(Part 10):2315–2326

    Article  PubMed  Google Scholar 

  54. Gilchrist J, Pericak-Vance M, Silverman L, Roses A (1988) Clinical and genetic investigation in autosomal dominant limb-girdle muscular dystrophy. Neurology 38(1):5–9

    Article  CAS  PubMed  Google Scholar 

  55. Shalaby S, Misuhashi H, Matsuda C, Minami N, Noguchi S, Nonaka I, Nishino I, Hayashi Y (2009) Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese limb girdle muscular dystrophy 1A patient. J Neuropathol Exp Neurol 68(6):701–707

    Article  CAS  PubMed  Google Scholar 

  56. Reilich P, Krause S, Schramm N, Klutzny U, Bulst S, Zehetmayer B, Schneiderat P, Walter MC, Schoser B, Lochmuller H (2011) A novel mutation in the myotilin gene (MYOT) causes a severe form of limb girdle muscular dystrophy 1A (LGMD1A). J Neurol 258(8):1437–1444

    Article  PubMed  Google Scholar 

  57. Hauser M, Conde C, Kowaljow V, Zeppa G, Taratuto A, Torian U, Vance J, Pericak-Vance M, Speer M, Rosa A (2002) Myotilin Mutation found in second pedigree with LGMD1A. Am J Hum Genet 71(6):1428–1432. https://doi.org/10.1086/344532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hauser M, Horrigan S, Salmikangas P, Torian U, Viles K, Dancel R, Tim R, Taivainen A, Bartoloni L, Gilchrist J, Stajich J, Gaskell P, Gilbert J, Vance J, Pericak-Vance M, Carpen O, Westbrook C, Speer M (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9(14):2141–2147

    Article  CAS  PubMed  Google Scholar 

  59. Garvey S, Miller S, Claflin D, Faulkner J, Hauser M (2006) Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM. Hum Mol Genet 15(15):2348–2362

    Article  CAS  PubMed  Google Scholar 

  60. Garvey S, Liu Y, Miller S, Hauser M (2008) Myotilin overexpression enhances myopathology in the LGMD1A mouse model. Muscle Nerve 37(5):663–667. https://doi.org/10.1002/mus.20994

    Article  CAS  PubMed  Google Scholar 

  61. Liu J, Wallace L, Garwick-Coppens S, Sloboda D, Davis C, Hakim C, Hauser M, Brooks S, Mendell J, Harper S (2014) RNAi-mediated $$ in LGMD1A Mi$$ce. Mol Ther Nucleic Acids 3:e160. https://doi.org/10.1038/mtna.2014.13

  62. Bonne G, Barletta MD, Varnous S, Becane H, Hammouda E, Merlini L, Mutoni F, Greenberg C, Gary F, Uritizberea J, Duboc D, Fardeau M, Toniolo D, Schwartz K (1999) Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet 21(3):285–288. https://doi.org/10.1038/6799

    Article  CAS  PubMed  Google Scholar 

  63. Muchir A, Bonne G, Avd K, Mv M, Baas F, Bolhuis P, Md V, Schwartz K (2000) Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet 9(9):1453–1459

    Article  CAS  PubMed  Google Scholar 

  64. Fatkin D, MacRae C, Sasaki T, Wolff M, Porcu M, Frenneaux M, Atherton J, Vidaillet H, Spudich S, Girolami UD, Seidman J, Seidman C, Mutoni F, Muehle G, Johnson W, McDonough B (1999) Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med 341(23):1715–1724

    Article  CAS  PubMed  Google Scholar 

  65. Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima N, Stewart C, Burke B (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147(5):913–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Stewart C, Kozlov S, Fong L, Young S (2007) Mouse models of the laminopathies. Exp Cell Res 313(10):2144–2156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kubben N, Voncken J, Konings G, van Weeghel M, van den Hoogenhof M, Gijbels M, van Erk A, Schoonderwoerd K, van den Bosch B, Dahlmans V, Calis C, Houten S, Misteli T, Pinto Y (2011) Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus 2(3):195–207. https://doi.org/10.4161/nucl.2.3.15731

    Article  PubMed  PubMed Central  Google Scholar 

  68. Angelini C (2014) Limb-girdle muscular dystrophy type 1C. In: Genetic neuromuscular disorders: a case-based approach. Springer International Publishing, Cham. https://doi.org/10.1007/978-3-319-07500-6

    Chapter  Google Scholar 

  69. Sunada Y, Ohi H, Hase A, Ohi H, Hosono T, Arata S, Higuchi S, Matsumura K, Shimizu T (2001) Transgenic mice expressing mutant caveolin-3 show severe my-opathy associated with increased nNOS activity. Hum Mol Genet 10(3):173–178

    Article  CAS  PubMed  Google Scholar 

  70. Woodman S, Park D, Cohen A, Cheung M, Chandra M, Shirani J, Tang B, Jelicks L, Kitsis R, Christ G, Factor S, Tanowitz H, Lisanti M (2002) Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade. J Biol Chem 277(41):38988–38997

    Article  CAS  PubMed  Google Scholar 

  71. Galbiati F, Engelman J, Volonte D, Zhang X, Minetti C, Li M, Hou H, Kneitz B, Edelmann W, Lisanti M (2001) Caveolin-3 Null Mice Show a Loss of Caveolae, Changesin the Microdomain Distribution of the Dystrophin-Glycoprotein Complex, and T-tubule Abnormalities. J Biol Chem 276(24):21425–21433. https://doi.org/10.1074/jbc.M100828200

    Article  CAS  PubMed  Google Scholar 

  72. Kramerova I, Beckmann J, Spencer M (2007) Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A). Biochim Biophys Acta 1772(2):128–144. https://doi.org/10.1016/j.bbadis.2006.07.002

    Article  CAS  PubMed  Google Scholar 

  73. Kramerova I, Kudryashova E, Venkatraman G, Spencer M (2005) Calpain 3 participates in muscle remodeling by acting upstream of the ubiquitin-proteasome pathway. Hum Mol Genet 14(15):2125–2134. https://doi.org/10.1093/hmg/ddi217

    Article  CAS  PubMed  Google Scholar 

  74. Kramerova I, Kudryashova E, Tidball J, Spencer M (2004) Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro. Hum Mol Genet 13(13):1378–1388. https://doi.org/10.1093/hmg/ddh153

    Article  CAS  Google Scholar 

  75. Fougerousse F, Gonin P, Durand M, Richard I, Raymackers J (2003) Force impairment in calpain 3-deficient mice is not correlated with mechanical disruption. Muscle Nerve 27(5):616–623. https://doi.org/10.1002/mus.10368

    Article  CAS  PubMed  Google Scholar 

  76. Ho M, Post CM, Donahue LR, Lidov HGW, Bronson RT, Goolsby H, Watkins SC, Cox GA, Brown RH (2004) Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency. Hum Mol Genet 13(18):1999–2010. https://doi.org/10.1093/hmg/ddh212

  77. Kobayashi K, Izawa T, Kuwamura M, Yamate J (2010) The distribution and characterization of skeletal muscle lesions in dysferlin-deficient SJL and A/J mice. Exp Toxicol Pathol 62(5):509–517. https://doi.org/10.1016/j.etp.2009.06.009

    Article  CAS  PubMed  Google Scholar 

  78. Kobayashi K, Izawa T, Kuwamura M, Yamate J (2012) Dysferlin and Animal Models for Dysferlinopathy. J Toxicol Pathol 25(2):135–147. https://doi.org/10.1293/tox.25.135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Duclos F, Straub V, Moore S, Venzke D, Hrstka R, Crosbie R, Durbeej M, Lebakken C, Ettinger A, van der Meulen J, Holt K, Lim L, Sanes J, Davidson B, Faulkner J, Wililamson R, Campbell K (1998) Progressive muscular dystrophy in α-sarcoglycan-deficient mice. J Cell Biol 142(6):1461–1471. https://doi.org/10.1083/jcb.142.6.1461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fanin M, Melacini P, Boito C, Pegoraro E, Angelini C (2003) LGMD2E patients risk developing dilated cardiomyopathy. Neuromuscul Disord 13(4):303–309

    Article  CAS  PubMed  Google Scholar 

  81. Pozsgai E, Griffin D, Heller K, Mendell J, Rodino-Klapac L (2016) β-Sarcoglycan gene transfer decreases fibrosis and restores force in LGMD2E mice. Gene Ther 23(1):57–66

    Article  CAS  PubMed  Google Scholar 

  82. Lopate G (2016) Limb-girdle muscular dystrophy. Medscape. http://emedicine.medscape.com/article/1170911-overview. Accessed Jan 2 2017

  83. Bushby K (2012) Limb-girdle muscular dystrophies. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/limb-girdle-muscular-dystrophies/. Accessed 10 Jan 2017

  84. Hack A, Lam M, Cordier L, Shoturma D, Ly C, Hadhazy M, Hadhazy M, Sweeney H, McNally E (2000) Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein complex. J Cell Sci 113(Pt 2):2532–2544

    Google Scholar 

  85. Nigro V, Moreira ES, Piluso G, Vainzof M, Belsito A, Politano L, Puca A, Passos-Bueno M, Zatz M (1996) Autosomal recessive limbgirdle muscular dystrophy, LGMD2F, is caused by a mutation in the δ-sarcoglycan gene. Nat Genet 14(2):195–198

    Article  CAS  PubMed  Google Scholar 

  86. Duggan D, Manchester D, Stears K, Mathews D, Hart C, Hoffman E (1997) Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limb-girdle muscular dystrophy (LGMD2). Neurogenetics 1(1):49–58

    Article  CAS  PubMed  Google Scholar 

  87. Homburger F, Baker J, Nixon C, Whitney R (1962) Primary, generalized polymyopathy and cardiac necrosis in an inbred line of Syrian hamsters. Med Express 6(5):339–345. https://doi.org/10.1159/000135178

    Article  Google Scholar 

  88. Holt K, Lim L, Straub V, Venzke D, Duclos F, Anderson R, Davidson B, Campbell K (1998) Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using delta-sarcoglycan gene transfer. Mol Cell 1(6):841–848

    Article  CAS  PubMed  Google Scholar 

  89. Toyo-Oka T, Kawada T, Nakata J, Xie H, Urabe M, Masui F, Ebisawa T, Tezuka A, Iwasawa K, Nakajima T, Uehara Y, Kumagai H, Kostin S, Schaper J, Nakazawa M, Ozawa K (2004) Translocation and cleavage of myocardial dystrophin as a common pathway to advanced heart failure: a scheme for the progression of cardiac dysfunction. Proc Natl Acad Sci U S A 101(19):7381–7385

    Article  PubMed  PubMed Central  Google Scholar 

  90. Mitsuhashi S, Saito N, Watano K, Igarashi K, Tagami S, Shima H, Kikuchi K (2003) Defect of δ-sarcoglycan gene is responsible for development of dilated cardiomyopathy of a novel hamster strain, J2N-k: calcineurin/PP2B activity in the heart of J2N-k hamster. J Biochem 132(2):269–276

    Article  CAS  Google Scholar 

  91. Hunter E, Hughes V, White J (1984) Cardiomyopathic hamsters, CHF 146 and CHF 147: a preliminary study. Can J Physiol Pharmacol 62(11):1423–1428

    Article  CAS  PubMed  Google Scholar 

  92. Coral-Vazquez R, Cohn R, Moore S, Hill J, Weiss R, Davisson R, Straub V, Barresi R, Bansal D, Hrstka R, Williamson R, Campbell K (1999) Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell 98(4):465–474

    Article  CAS  PubMed  Google Scholar 

  93. Nomura T, Ashihara E, Tateishi K, Asada S, Ueyama T, Takahashi T, Matsubara H, Oh H (2007) Skeletal myosphere-derived progenitor cell transplantation promotes neovascularization in δ-sarcoglycan knockdown cardiomyopathy. Biochem Biophys Res Commun 352(3):668–374

    Article  CAS  PubMed  Google Scholar 

  94. Shelton G, Engvall E (2005) Canine and feline models of human inherited muscle diseases. Neuromuscul Disord 15(2):127–138

    Article  PubMed  Google Scholar 

  95. Schatzberg S (2003) Sarcoglycanopathy in 3 dogs. In: Proceedings of the American College of Veterinary Internal Medicine. American College of Veterinary Internal Medicine, Dallas

    Google Scholar 

  96. Saccone V, Palmieri M, Passamano L, Piluso G, Meroni G, Politano L, Nigro V (2008) Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Hum Mutat 29(2):240–247

    Article  CAS  PubMed  Google Scholar 

  97. Frosk P, Greenberg C, Tennese A, Lamont R, Nylen E, Hirst C, Frappier D, Roslin N, Zaik M, Bushby K, Straub V, Zatz M, de Paula F, Morgan K, Fujiwara T, Wrogemann K (2005) The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations. Hum Mutat 25(1):38–44. https://doi.org/10.1002/humu.20110

    Article  CAS  PubMed  Google Scholar 

  98. Beltran-Valero de Bernabé D, Voit T, Longman C, Steinbrecher A, Straub V, Yuva Y, Herrmann R, Sperner J, Korenke C, Diesen C, Doboyns W, Brunner H, van Bokhoven H, Brockington M, Muntoni F (2004) Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet 41(5):e61

    Article  PubMed  Google Scholar 

  99. Boito C, Melacini P, Vianello A, Prandini P, Gavassini B, Bagattin A, Siciliano G, Angelini C, Pegoraro E (2005) Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 62(12):1894–1899. https://doi.org/10.1001/archneur.62.12.1894

    Article  PubMed  Google Scholar 

  100. Ackroyd M, Skordis L, Kluarachchi M, Godwin J, Prior S, Fidanboylu M, Piercy R, Mutoni F, Brown S (2009) Reduced expression of fukutin related protein in mice results in a model for fukutin related protein associated muscular dystrophies. Brain 132:439–451. https://doi.org/10.1093/brain/awn335

    Article  CAS  PubMed  Google Scholar 

  101. Wang C, Chan Y, Tang R, Xiao B, Lu P, Keramaris-Vrantsis E, Zheng H, Qiao C, Jiang J, Li J, Ma H, Lu Q, Xiao X (2011) Post-natal knockdown of fukutin-related protein expression in muscle by long-term RNA interference induces dystrophic pathology. Am J Pathol 178(1):261–272. https://doi.org/10.1016/j.ajpath.2010.11.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Blaeser A, Keramaris E, Chan Y, Sparks S, Cowley D, Xiao X, Lu Q (2013) Mouse models of fukutin-related protein mutations show a wide range of disease phenotypes. Hum Genet 132(8):923–934. https://doi.org/10.1007/s00439-013-1302-7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    Stephanie M. Shrader

  2. Opelika, AL, USA

    Roberta Wrighten

  3. Department of Pathobiology, Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA

    Bruce F. Smith

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  1. Stephanie M. Shrader
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  2. Roberta Wrighten
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  3. Bruce F. Smith
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Correspondence to Stephanie M. Shrader .

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Editors and Affiliations

  1. Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA, Department of Biomedical Sciences College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Department of Bioengineering, University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  2. Department of Pediatrics Nationwide Children’s Hospital and Research Institute, Department of Neurology Nationwide Children’s Hospital and Research Institute, The Ohio State University, Columbus, OH, USA

    Jerry R. Mendell

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Shrader, S.M., Wrighten, R., Smith, B.F. (2019). Animal Models for Muscle Disease and Muscle Gene Therapy. In: Duan, D., Mendell, J. (eds) Muscle Gene Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-03095-7_3

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