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Animal models for scoliosis research: state of the art, current concepts and future perspective applications

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Abstract

Purpose

The purpose of this study was to provide the readers with a reliable source of animal models currently being utilized to perform state-of-the-art scoliotic research.

Materials and methods

A comprehensive search was undertaken to review all publications on animal models for the study of scoliosis within the database from 1946 to January 2011.

Results

The animal models have been grouped under specific headings reflecting the underlying pathophysiology behind the development of the spinal deformities produced in the animals: genetics, neuroendocrine, neuromuscular, external constraints, internal constraints with or without tissue injury, vertebral growth modulation and iatrogenic congenital malformations, in an attempt to organize and classify these multiple scoliotic animal models. As it stands, there are no animal models that mimic the human spinal anatomy with all its constraints and weaknesses, which puts it at risk of developing scoliosis. What we do have are a multitude of models, which produce spinal deformities that come close to the idiopathic scoliosis deformity.

Conclusion

All these different animal models compel us to believe that the clinical phenotype of what we call idiopathic scoliosis may well be caused by a variety of different underlying pathologies.

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References

  1. Arkin AM (1949) The mechanism of structural changes in scoliosis. J Bone Joint Surg Br 66:519–528

    Google Scholar 

  2. Dickson RA, Lawton JO, Archer IA et al (1984) The pathogenesis of idiopathic scoliosis. Biplanar spinal asymmetry. J Bone Joint Surg Br 66:8–15

    PubMed  CAS  Google Scholar 

  3. Murray DW, Bulstrode CJ (1996) The development of adolescent idiopathic scoliosis. Eur Spine J 5:251–257

    Article  PubMed  CAS  Google Scholar 

  4. Couturier J, Rault D, Cauzinille L (2008) Chiari malformation and syringomyelia in normal cavalier King Charles Spaniels. A multiple diagnostic imaging approach. J Small Animal Prac 49:438–443

    Article  CAS  Google Scholar 

  5. Von Lesser L (1888) Experimentelles und Klinischeses über Skoliose. Virchows Arch 113:10–46

    Article  Google Scholar 

  6. Nachlas IW, Borden JN (1950) Experimental scoliosis; the role of the epiphysis. Surg Gynecol Obstet 90(6):672–680

    PubMed  CAS  Google Scholar 

  7. Sawin PB, Crary DD (1964) Genetics of skeletal deformities in the domestic rabbit (Oryctolagus cuniculus). Clin Orthop Relat Res 33:71–90

    Article  PubMed  CAS  Google Scholar 

  8. Carrey M (1981) Genetics of scoliosis in chicken. J Hered 72:6–12

    Google Scholar 

  9. Janssen MA, de Wilde RF, Kouwenhoven JM, Castelein RM (2011) Experimental models in scoliosis research: a review of the literature. Spine 11:347–358

    Article  Google Scholar 

  10. Mc Ewen GD (1973) Experimental scoliosis. Clin Orthop Relat Res 93:69–74

    Article  Google Scholar 

  11. Raggio CL, Giampietro PF et al (2009) A novel locus for adolescent idiopathic scoliosis on chromosome 12p. J Orthop Res 27(10):1366–1372

    Article  PubMed  Google Scholar 

  12. Giampeietro PF, Raggio CL et al (2006) DLL3 as a candidate gene for vertebral malformations. Am J Med Genet Part A. 140(22):2447–2453

    Google Scholar 

  13. Giampietro PF, Blank RD et al (2003) Congenital and idiopathic scoliosis. Clinical and genetic aspects. Clin Med Res 1(2):125–136

    Article  PubMed  Google Scholar 

  14. Blanco G, Coulton GR et al (2001) The kyphoscoliotic (ky) mouse is deficient in hypertrophic responses and is caused by a mutation in a novel muscle specific protein. Hum Mol Genet 10(1):9–16

    Article  PubMed  CAS  Google Scholar 

  15. Gorman KF, Tredwell SJ, Breden F (2007) The mutant guppy syndrome curveback as a model for human heritable spinal curvature. Spine 32(7):735–741

    Article  PubMed  Google Scholar 

  16. Gorman KF, Handrigan GR et al (2010) Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model. Scoliosis 7:5–10

    Google Scholar 

  17. Gorman KF, Christians JK et al (2011) A major QTL controls susceptibility to spinal curvature in the curveback guppy. BMC genet 12(1):16

    Article  PubMed  Google Scholar 

  18. Qiu XS, Tang NL et al (2007) Melatonin receptor 1B(MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 32(16):1748–1753

    Article  PubMed  Google Scholar 

  19. Thillard MJ (1959) Vertebral column deformities following epiphysectomy in the chick. CR Hebd seances Acad Sci 248:1238–1240

    CAS  Google Scholar 

  20. Dubousset J, Queneau P, Thillard M (1983) Experimental scoliosis induced by pineal and diencephalic lesions in young chickens: its relation with clinical findings. Orthop Trans 7:7–12

    Google Scholar 

  21. Machida M, Dubousset J, Imamura Y et al (1994) Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patient with idiopathic scoliosis. J Pediatr Ortop 14:329–335

    Article  CAS  Google Scholar 

  22. Machida M, Dubousset J, Imamura Y et al (1995) Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens. J Bone Joint Surg Br 77:134–138

    PubMed  CAS  Google Scholar 

  23. Machida M, Murai I et al (1999) Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine 24:1985–1989

    Article  PubMed  CAS  Google Scholar 

  24. O’Kelly C, Wang X et al (1999) The production of scoliosis after pinealectomy in young chickens, rats, and hamsters. Spine 24:35–43

    Article  PubMed  Google Scholar 

  25. Cheung KM, Wang T et al (2005) The effect of pinaelectomy on scoliosis development in young nonhuman primates. Spine 30:2009–2013

    Article  PubMed  Google Scholar 

  26. Day GA, Mc Phee IB et al (2007) Idiopathic scoliosis and pineal lesions in Australian children. J Orthop Surg (Hong-Kong) 15(3):327–333

    CAS  Google Scholar 

  27. Grivas TB, Savvidou OD (2007) Melatonin the “light of night” in human biology and adolescent idiopathic scoliosis. Scoliosis 2:6

    Article  PubMed  Google Scholar 

  28. Oyama J, Murai I et al (2006) Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels. J Pineal Res 40:219–224

    Article  PubMed  CAS  Google Scholar 

  29. Machida M, Dubousset J, Yamada T, Kimura J, Saito M, Shiraishi T, Yamagishi M (2006) Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy. J Pineal Res 41(1):1–7

    Google Scholar 

  30. Akel I, Demirkiran G et al (2009) The effect of calmodulin antagonist on scoliosis: bipedal C57BL/6J mice model. Eur Spine J 18:499–505

    Article  PubMed  Google Scholar 

  31. Girardo M, Bettini N et al (2011) The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS). Eur Spine J 20(1):S68–S74

    Article  PubMed  Google Scholar 

  32. Wang S, Qiu Y et al (2007) Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis. J Orthop Surg 2:19

    Article  Google Scholar 

  33. MacEwen GD (1973) Experimental scoliosis. Isr J Med Sci 6:714–718

    Google Scholar 

  34. Suk SI, Song HS et al (1989) Scoliosis induced by anterior and posterior rhizotomy. Spine 14:692–697

    Article  PubMed  CAS  Google Scholar 

  35. Pincott JR, Taffs LF (1982) Experimental scoliosis in primates: a neurological cause. J Bone Joint Surg Br 64:503–507

    PubMed  CAS  Google Scholar 

  36. Pincott JR, Davies JS et al (1984) Scoliosis caused by section of dorsal spinal nerve roots. J Bone Joint Surg Br 66:27–29

    PubMed  CAS  Google Scholar 

  37. Lambert FM, Malinvaud D et al (2009) Vestibular asymmetry as the cause of idiopathic scoliosis: a possible answer from Xenopus. J Neurosci 29:12477–12483

    Article  PubMed  CAS  Google Scholar 

  38. De Waele C, Graf W et al (1989) A radiological analysis of the postural syndromes following hemilabyrinthectomy and selective canal and otolith lesions in the guinea pig. Exp Brain Res 77(1):166–182

    Article  PubMed  Google Scholar 

  39. Dieringer N (1995) “Vestibular compensation”: neural plasticity and its relations to functional recovery after labyrinthine lesions in frogs and other vertebrates. Prog Neurobiol 46(2–3):97–129

    PubMed  CAS  Google Scholar 

  40. Mason RM, Palfrey AJ (1984) Intervertebral disc degeneration in adult mice with hereditary kyphoscoliosis. J Orthop Res 2(4):333–338

    Article  PubMed  CAS  Google Scholar 

  41. Blanco G, Coulton GR et al (2001) The kyphoscoliosis (ky) mouse is deficient in hypertrophic responses and is caused by a mutation in a novel muscle-specific protein. Hum Mol Genet 10(1):9–16

    Article  PubMed  CAS  Google Scholar 

  42. Roaf R (1966) The basic anatomy of scoliosis. J Bone Joint Surg Br 48:786–792

    PubMed  CAS  Google Scholar 

  43. Dickson RA (1988) The aetiology of spinal deformities. Lancet 331:1151–1155

    Article  Google Scholar 

  44. Poussa M, Schlenzka D, Ritsilä V (1991) Scoliosis in growing rabbits induced with an extension splint. Acta Ortop Scand 62:136–138

    Article  CAS  Google Scholar 

  45. Hakkarainen S (1981) Experimental scoliosis: production of structural scoliosis by immobilization of young rabbits in a scoliotic position. Acta Orthop Scand Suppl 192:1–57

    PubMed  CAS  Google Scholar 

  46. Wynarsky G, Schultz A (1987) Effects of age and sex on the external induction of scoliosis in rats. Spine 12(10):974–977

    Article  PubMed  CAS  Google Scholar 

  47. Mente PL, Stokes IA et al (1997) Progression of vertebral wedging in an asymmetrically loaded rat tail model. Spine 22:1292–1296

    Article  PubMed  CAS  Google Scholar 

  48. Stokes IA, Spence H et al (1996) Mechanical modulation of vertebral body growth. Implications for scoliosis progression. Spine 21:1162–1167

    Article  PubMed  CAS  Google Scholar 

  49. Aronsson DD, Stokes IA et al (2010) The role of remodeling and asymmetric growth in vertebral wedging. Stud Health Technol Inform 158:11–15

    PubMed  Google Scholar 

  50. Stokes IA, Mc Bride CA et al (2008) Intervertebral disc changes in an animal model representing altered mechanics in scoliosis. Stud Health Tech Inform 140:273–277

    CAS  Google Scholar 

  51. Kalleimeier PM, Buttermann GR et al (2006) Validation, reliability, and complications of a tethering scoliosis model in the rabbit. Eur Spine J 15:449–456

    Article  Google Scholar 

  52. Sarwark JF, Dabney KW et al (1988) Experimental scoliosis in the rat. I. Methodology, anatomic features and neurologic characterization. Spine 13:466–471

    Article  PubMed  CAS  Google Scholar 

  53. Somerville EW (1952) Rotational lordosis; the developmentof single curve. J Bone Joint Surg Br 34-B:421–427

    Google Scholar 

  54. Liu L, Zhu Y et al (2011) The creation of scoliosis by scapula-to-contralateral ilium tethering procedure in bipedal rats: a kyphoscoliosis model. Spine 36(17):1340–1349

    Article  PubMed  Google Scholar 

  55. Sevastikoglou JA, Aaro S et al (1978) Experimental scoliosis in growing rabbits by operations on the rib cage. Clin Orthop Related Res 136:282–286

    Google Scholar 

  56. Sevastik B, Agadir M et al (1990) Vascular changes in the chest wall after unilateral resection of the intercostal nerves in the growing rabbit. J Orthop Res 8:283–290

    Article  PubMed  Google Scholar 

  57. Sevastik J, Agadir M, Sevastik B (1990) Effects of rib elongation on the spine. II. Correction of scoliosis in the rabbit. Spine 15(8):826–829

    Google Scholar 

  58. Langenskiold A, Michelsson JEA (1962) Experimental progressive scoliosis. Acta Orthop Scand Suppl 59:1–26

    PubMed  CAS  Google Scholar 

  59. Alexander MABunch WH et al (1972) Can experimental dorsal rhizotomy produce scoliosis? J Bone Joint Surg Am 54:1509–1513

    Google Scholar 

  60. Barrios C, Tuñón MT, De Salis JA, Beguiristain JL, Cañadell J (1987) Scoliosis induced by medullary damage: an experimental study in rabbits. Spine (Phila Pa 1976) 12(5):433–439

    Google Scholar 

  61. Robin GC, Stein H (1975) Experimental scoliosis in primates. Failure of a technique. J Bone Joint Surg Br 57(2):142–145

    Google Scholar 

  62. Thomas S, Dave PK (1985) Experimental scoliosis in monkeys. Acta Orthop Scand 56:43–46

    Article  PubMed  CAS  Google Scholar 

  63. Metha HP, Snyder BD et al (2010) Expansion thoracoplasty improves respiratory function in a rabbit model of postnatal pulmonary hypoplasia: a pilot study. Spine 35(2):153–161

    Article  Google Scholar 

  64. Olson JC, Kurek KC et al (2011) Expansion thoracoplasty affects lung growth and morphology in a rabbit model: a pilot study. Clin Orthop Relat Res 469(5):1375–1382

    Article  PubMed  Google Scholar 

  65. Beguiristain JL, De Salis J et al (1980) Experimental scoliosis by epiphysiodesis in pigs. Int Orthop 3:317–321

    Article  PubMed  CAS  Google Scholar 

  66. Zhang H, Sucato DJ et al (2008) Neurocentral synchondrosis screw epiphysiodesis of the neurocentral synchondrosis. Production of idiopathic-like scoliosis in an immature animal model. J Bone Joint Surg Am 90:2460–2469

    Article  PubMed  Google Scholar 

  67. Zhang H, Sucato DJ (2010) Neurocentral synchondrosis screws to create and correct experimental deformity: a pilot study. Clin Orthop Relat Res 469(5):1383–1390

    Article  Google Scholar 

  68. Zhang H, Sucato DJ (2011) Anterior vs posterior approach of neurocentral cartilage hemiepiphysiodesis to create experimental scoliosis. 19th IMAST congress Copenhagen

  69. Newton PO, Farnsworth CL et al (2008) Spinal growth modulation with an anterolateral flexible tether in an immature bovine model: disc health and motion preservation. Spine 33:724–733

    Article  PubMed  Google Scholar 

  70. Braun JT, Ogilvie JW, Akyuz E, Brodke DS, Bachus KN, Stefko RM (2003) Experimental scoliosis in an immature goat model: a method that creates idiopathic‐type deformity with minimal violation of the spinal elements along the curve. Spine (Phila Pa 1976) 28(19):2198–2203

    Google Scholar 

  71. Braun JT, Ogilvie JW (2003) Experimental scoliosis in an immature goat model: a method that creates idiopathic-type deformity with minimal violation of the spinal elements along the curve. Spine 28:2198–2203

    Article  PubMed  Google Scholar 

  72. Braun JT, Ogilvie et al (2006) Creation of an experimental idiopathic-type scoliosis in an immature goat model using a flexible posterior asymmetric tether. Spine 31(13):1410–1414

  73. Schwab F, Patel A et al (2009) A porcine model for progressive thoracic scoliosis. Spine 34:E397–E404

    Article  PubMed  Google Scholar 

  74. Zhang YG, Zheng GQ et al (2009) Scoliosis model created by pedicle screw tethering in an immature goats: the feasibility, reliability, and complications. Spine 34:2305–2310

    Article  PubMed  Google Scholar 

  75. Odent T, Cachon T (2011) Porcine model of early onset scoliosis based on animal growth created with mini-invasive posterior offset tethering: a preliminary report. Eur Spine J 20(11):1869–1876

    Article  PubMed  Google Scholar 

  76. Patel A, Schwab F et al (2011) Does removing the spinal tether in a porcin scoliosis model result in persistent deformity? A pilot study. Clin Orthop Relat Res 469(5):1368–1374

    Article  PubMed  Google Scholar 

  77. Rivard C (1982) Chir Pedia

  78. Farley FA, Hall J et al (2006) Characteristics of congenital scoliosis in a mouse model. J Pediatr Orthop 26:341–346

    Article  PubMed  Google Scholar 

  79. Fei Q, Wu Z et al (2010) The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population. Spine 35(9):98308

    Article  Google Scholar 

  80. Goshu E, Jin H et al (2002) Sim@ mutants have developmental defects not overlapping with those of Sim1 mutants. Mol Cell Biol 22(12):4147–4157

    Article  PubMed  CAS  Google Scholar 

  81. Seifert J, Bell et al (2011) Characterization of a novel bidirectional distraction spinal cord injury animal model. J Neurosci Meth 197(1):97–103

    Article  CAS  Google Scholar 

  82. Salehi LB, Mangino M et al (2002) Assignment of a locus for autosomal dominant idiopathic scoliosis to human chromosome 17p11. Human Genet 111:401–404

    Article  CAS  Google Scholar 

  83. Mahood JK, Jiang H et al (1997) Melatonin levels in idiopathic scoliosis. Spine 21:1974–1978

    Google Scholar 

  84. Sahlstrand T, Petruson B (1979) A study of labyrinthine function in patietns with adolescent idiopathic scoliosis. An electro-nystagmographic study. Acta Orthop Scan 50:759–769

    Article  CAS  Google Scholar 

  85. Mallau S, Bollini G et al (2007) Locomotor skills and balance strategies in adolescents idiopathic scoliosis. Spine 32:E14–E22

    Article  PubMed  Google Scholar 

  86. Wiener-Vacher SR, Mazda K (1998) Asymmetric otolith vestibulo-occular responses in children with idiopathic scoliosis. J Pediatr 132(6):1028–1032

    Article  PubMed  CAS  Google Scholar 

  87. Sahlstrand T, Petruson B (1979) A study of labyrinthine function in patients with idiopathic scoliosis. I. An electro-nystagmographic study. Acta Ortop Scand 50(6):759–769

    Article  CAS  Google Scholar 

  88. Alini M, Eisenstin SM et al (2008) Are animal models useful for studying human disc disorders/degeneration? Eur Spine J17:2–19

    Article  Google Scholar 

  89. White AA, Panjabi MM (1990) Clinical biomechanics of the spine. 2nd edn. JB Lippincott Company

  90. Nachlas IW, Borden JN (1950) Experimental scoliosis; the role of the epiphysis. Surg Gynecol Obstet 90(6):672–680

    PubMed  CAS  Google Scholar 

  91. Braun JT, Ogilvie JW et al (2004) Fusionless scoliosis correction using a shape memory alloy staple in the anterior thoracic spine of the immature goat. Spine 29:1980–1989

    Article  PubMed  Google Scholar 

  92. Braun JT, Akyuz E et al (2006) Three-dimensional analysis of 2 fusionless scoliosis treatment: a flexible ligament tether versus a rigid-shape memory alloy staple. Spine 31:262–268

    Article  PubMed  Google Scholar 

  93. Lafage V, Schwab V et al (2011) Three dimensions corrections of scoliosis in a porcine model with an anterolateral tethering correction surgical device. 19th IMAST congress Copenhagen

  94. Wilke HJ, Kettler et al (1999) Is the lumbar sheep spine an adequate model for the human spine? A comparison of biomechanical properties, macroscopic and microscopic anatomy and bone mineral density. In proceedings of the 26th annual meeting, Hawaii, p 24

  95. D’Aout K, Aerts P et al (2002) Segment and joint angles of hind limb during bipedal and quadrupedal walking of the bonobo. Am J Phys Anthrop 119(37):51

    Google Scholar 

  96. Castelein RM, van Dieen JH et al (2005) The role of dorsal shear forces in the pathogenesis of adolescent idiopathic scoliosis: a hypothesis. Med Hypothesis 65:501–508

    Article  Google Scholar 

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Acknowledgment

The institution of the author receives fellowship research funding from AO Spine North America unrelated to this work. The author has had commercial associations in the form of contractual consultancies work with Synthes.

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Correspondence to Jean Ouellet.

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Ouellet, J., Odent, T. Animal models for scoliosis research: state of the art, current concepts and future perspective applications. Eur Spine J 22 (Suppl 2), 81–95 (2013). https://doi.org/10.1007/s00586-012-2396-7

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  • DOI: https://doi.org/10.1007/s00586-012-2396-7

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