Aphanius fasciatus: a molecular model of scoliosis?


Study design

Observational study of Killifish with spinal deformities


To evaluate the morphology and molecular biology of Aphanius fasciatus with severe spine deformities.

Summary of background data

Idiopathic Scoliosis affects 3% of the population and is an abnormal three-dimensional curvature of the spine with unknown cause. The lack of a model system with naturally occurring spinal curvatures has hindered research on the etiology of IS.


The Mediterranean killifish Aphanius fasciatus, collected from the coast of Sfax (Tunisia), which has an inborn skeletal deformity was chosen. We used morphologic features to evaluate the severity of scoliosis according to the different types and performed a biochemical analysis using factors previously studied in humans (estradiol, melatonin and Insulin Growth Factor 1 “IGF-1”).


We have detected relevant molecular deviations that occur in Killifish deformities and the fish with severe scoliosis are smaller and less old than the ones with milder scolioses. Furthermore, a significant change in levels of ovarian estradiol, liver IGF-1 and brain melatonin was noted between deformed and normal fish.


Aphanius fasciatus could be used as a molecular model system to study the etiology of IS in humans as the characterization of the Aphanius fasciatus scoliosis syndrome has revealed morphological and biochemical parallels to IS. However, it is important to note the limitations of the proposed model, including the short lifespan of the fish.

Level of evidence


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  1. 1.

    Kristen F, Gorman BSc, Felix B (2009) Idiopathic-type scoliosis is not exclusive to bipedalism. Med Hypotheses 72(3):348–352

  2. 2.

    Yamada S, Yamamoto T, Tonomura Y (1970) Reaction mechanism of the Ca2 plus-dependent ATPase of sarcoplasmic reticulum from skeletal muscle. 3. Ca plus-uptake and ATP-splitting. J Biochem 67(6):789–794

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Burwell RG, Cole AA, Cook TA et al (1992) Pathogenesis of idiopathic scoliosis. The Nottingham concept. Acta OrthopBelg 58(Suppl 1):33–58

    Google Scholar 

  4. 4.

    Machida M (1999) Cause of idiopathic scoliosis. Spine (Phila Pa 1976) 24(24):2576–2583

    CAS  Article  Google Scholar 

  5. 5.

    Machida M, Weinstein SL, Yamada T et al (1985) Spinal cord monitoring. Electrophysiological measures of sensory and motor function during spinal surgery. Spine (Phila Pa 1976) 10(5):407–413

    CAS  Article  Google Scholar 

  6. 6.

    Castelein RM, van Dieën JH, Smit TH (2005) The role of dorsal shear forces in the pathogenesis of adolescent idiopathic scoliosis—a hypothesis. Med Hypotheses 65(3):501–508

    PubMed  Article  Google Scholar 

  7. 7.

    Xiao J, Wu ZH, Qiu GX et al (2007) Upright posture impact on spine susceptibility in scoliosis and progression patterns of scoliotic curve. Zhonghua Yi XueZaZhi 87(1):48–52

    Google Scholar 

  8. 8.

    Kawakami M, Tamaki T, Yoshida M et al (1999) Axial symptoms and cervical alignments after cervical anterior spinal fusion for patients with cervical myelopathy. J Spinal Disord 12(1):50–56

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Gorman KF, Breden F (2009) Idiopathic-type scoliosis is not exclusive to bipedalism. Med Hypotheses 72(3):348–352

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    O’Kelly C, Wang X, Raso J et al (1999) The production of scoliosis after pinealectomy in young chickens, rats, and hamsters. Spine (Phila Pa 1976) 24(1):35–43

    CAS  Article  Google Scholar 

  11. 11.

    Cheung KM, Wang T, Poon AM et al (2005) The effect of pinealectomy on scoliosis development in young nonhuman primates. Spine (Phila Pa 1976) 30(18):2009–2013

    Article  Google Scholar 

  12. 12.

    Lowe TG, Edgar M, Margulies JY et al (2000) CH.Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 82-A(8):1157–1168

    Article  Google Scholar 

  13. 13.

    Fjelldal PG, Grotmol S, Kryvi H et al (2004) Pinealectomy induces malformation of the spine and reduces the mechanical strength of the vertebrae in Atlantic salmon Salmo salar. J Pineal Res 36(2):132–139

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Antunes M, Da Lopes CP (2002) Skeletal anomalies in Gobiusniger (Gobiidae)from Sado Estuary. Portugal Cybium 26:179–184

    Google Scholar 

  15. 15.

    Messaoudi I, Kessabi K, Kacem A et al (2009) Incidence of spinal deformities in natural populations of Aphaniusfasciatus Nardo, 1827 from the Gulf of Gabes Tunisia. Afr J Ecol 47:360–366

    Article  Google Scholar 

  16. 16.

    Gorman KF, Breden F (2010) Disproportionate body lengths correlate with idiopathic-type curvature in the curve back guppy. Spine (Phila Pa 1976) 35(5):511–516

    Article  Google Scholar 

  17. 17.

    Kristen F, Gorman BSc, Stephen J et al (2007) The Mutant Guppy Syndrome Curveback as a Model for Human Heritable Spinal Curvature. Spine 32(7):735–74

  18. 18.

    Boumaïza M, Quinard J, Ktari M (1979) Contribution à la biologie de la reproduction d’Aphanius fasciatus Nardo, 1827 (Pisces: Cyprinodontidae) de Tunisie. Bull Off Natl Pesches Tunis 3:221–240

    Google Scholar 

  19. 19.

    Villwock W (1982) Aphanius (Nardo, 1827) and Cyprinodon (Lac., 1803) (Pisces: Cyprinodontidae), an attempt for genetic interpretation of speciation. Z ZoologSystEvolforsch 20:187–197

  20. 20.

    CGP (1996) Annuaire des statistiques des pêches en Tunisie. Ministère de l’agriculture, Tunisie

    Google Scholar 

  21. 21.

    Kessabi K, Kerkeni A, Saïd K, Messaoudi I (2009) Involvement of Cd bioaccumulation in spinal deformities occurrence in natural populations of Mediterranean killifish. Biol Trace Element Res 128:72–81

    CAS  Article  Google Scholar 

  22. 22.

    Kessabi K, Annabi A, Hassine AI et al (2013) Possible chemical causes of skeletal deformities in natural populations of Aphaniusfasciatus collected from the Tunisian coast. Chemosphere (90)2683–2689

  23. 23.

    Kessabi K, Said K, Messaoudi I (2013) Comparative study of longevity, growth, and biomarkers of metal detoxication and oxidative stress between normal and deformed Aphaniusfasciatus (Pisces, Cyprinodontidae). J Toxicol Environ Health Part A 76:1269–1281

    CAS  Article  Google Scholar 

  24. 24.

    Zhang J, Edmond L, Lawrence H et al (2009) Automatic Cobb Measurement of Scoliosis Based on Fuzzy Hough Transform with Vertebral Shape Prior. J Digital Imaging 22:463–472

    Article  Google Scholar 

  25. 25.

    Justin DB, David GL, Randolph G et al (2015) Animal models of scoliosis. Orthop Res 33:458–467

    Article  Google Scholar 

  26. 26.

    Bradley JB, Jennifer AM, Yasmin SM et al (2012) Avian intervertebral disc arises from rostral sclerotome and lacks a nucleus pulposus: implications for evolution of the vertebrate disc. Dev Dynam 241:675–683

    Article  CAS  Google Scholar 

  27. 27.

    Wojcik G, Piskorz J, Ilzecka J et al (2014) Effect of intervertebral disc disease on scoliosis in the lumbar spine. Curr Issues Pharm Med Sci 27:155–158

    Google Scholar 

  28. 28.

    Nakhaee K, Tavakoli GA, Abedi R (2019) Relationship between intervertebral disc morphology and adolescent idiopathic scoliosis. Clin Eng 44(4):174–179

    Article  Google Scholar 

  29. 29.

    Kessabi K, Hwas Z, Sassi A, Said K et al (2014) Heavy metal accumulation and histomorphological alterations in Aphanius fasciatus (Pisces, Cyprinodontidae) from the Gulf of Gabes (Tunisia). Environ Sci Pollut Res Int 21(24):14099–14109

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Tomasiewicz HG, Johnson BA, Liu XC et al (2017) Development of Zebrafish (Danio rerio) as a natural model system for studying scoliosis. J OrthopSurgRehabil 1–1

  31. 31.

    Ioannis L, Apostolos S (1999) Population age and sex structure of Aphaniusfasciatus Nardo, 1827 (Pisces: Cyprinodontidae) in the Mesolongi and Etolikon lagoons (W. Greece). Fish Res 40(1999):227–235.

  32. 32.

    Mao SH, Jiang J, Sun X et al (2011) Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature. Eur Spine J 20(2):260–265

    PubMed  Article  Google Scholar 

  33. 33.

    Tutman P, Glamuzina B, Skaramuca B et al (2000) Incidence of spinal deformities in natural populations of sand smelt, Atherinaboyeri (Risso, 1810) in the Neretva River estuary, middle Adriatic. Fish Res 45:61–64

    Article  Google Scholar 

  34. 34.

    Annabi A, Saïd K, Messaoudi I (2013) Heavy metal levels in gonad and liver tissues effects on the reproductive parameters of natural populations of Aphanius facsiatus. Environ SciPollut Res 20(10):7309–7319

    CAS  Article  Google Scholar 

  35. 35.

    Leboeuf D, Letellier K, Alos N et al (2009) Do estrogens impact adolescent idiopathic scoliosis. Trends EndocrinolMetab 20(4):147–152

    CAS  Article  Google Scholar 

  36. 36.

    Aleksandra K, Anna G, Jagoda D et al (2015) Participation of sex hormones in multifactorial pathogenesis of adolescent idiopathic scoliosis. Int Orthopaedics (SICOT) 39:1227–1236

    Article  Google Scholar 

  37. 37.

    Esposito T, Uccello R, Caliendo R et al (2009) Estrogen receptor polymorphism, estrogen content and idiopathic scoliosis in human: a possible genetic linkage. J Steroid BiochemMolBiol 116(1–2):56–60

    CAS  Article  Google Scholar 

  38. 38.

    Zhou C, Wang H, Zou Y et al (2015) Research progress of role of estrogen and estrogen receptor on onset and progression of adolescent idiopathic scoliosis. ZhongguoXiu Fu Chong Jian WaiKeZaZhi 29:1441–1445

    CAS  Google Scholar 

  39. 39.

    Sanders JO, Browne RH, Cooney TE et al (2009) Correlates of the peak heightvelocity in girls with idiopathic scoliosis. Spine (Phila Pa 1976) 31(20):2289–2295

    Article  Google Scholar 

  40. 40.

    Khosla S, Oursler MJ, Monroe DG (2012) Estrogen and the skeleton. Trends EndocrinolMetab. 23(11):576–81

  41. 41.

    Suzuki N, Hayakawa K, Kameda T et al (2009) Monohydroxylated polycyclic aromatic hydrocarbons inhibit both osteoclastic and osteoblastic activities in teleost scales. Life Sci 84:482–488

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Kitajima Y, Ono Y (2016) Estrogens maintain skeletal muscle and satellite cell functions. J Endocrinol 229(3):267–275

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Le G, Novotny SA, Mader TL et al (2018) A moderate oestradiol level enhances neutrophil number and activity in muscle after traumatic injury but strength recovery is accelerated. J Physiol 596(19):4665–4680

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Wang J, Zhou J, Bondy CA (1999) Igf1 promotes longitudinal bone growth by insulin-like actions Augmenting chondrocyte hypertrophy. FASEB J 13(14):1985–1990

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Faria P, Joice BF, Diego B (2011) Melatonin as a central molecule connecting neural development and calcium signaling. Funct Integr Genomics 11(3):383–388

    Article  CAS  Google Scholar 

  46. 46.

    Brzezinski A (1997) Melatonin in humans. N Engl J Med 36(3):186–195

    Article  Google Scholar 

  47. 47.

    Cardinali DP, García AP, Cano P, Esquifino AI (2004) Melatonin role in experimental arthritis. Curr Drug Targets Immune EndocrMetabolDisord 4(1):1–10

    CAS  Article  Google Scholar 

  48. 48.

    Thillard MJ (1959) Vertebral column deformities following epiphysectomy in the chick. C R Hebd Seances Acad Sci 248(8):1238–1240

    CAS  PubMed  Google Scholar 

  49. 49.

    Machida M, Dubousset J, Imamura Y et al (1996) Melatonin. A possible role in pathogenesis of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 21(10):1147–1152

    CAS  Article  Google Scholar 

  50. 50.

    Satomura K, Tobiume S, Tokuyama R et al (2007) Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. J Pineal Res 42:231–239

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Maria S, Samsonraj RM, Munmun F et al (2018) Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. J Pineal Res 64(3)

  52. 52.

    Kesling KL, Reinker KA (1997) A meta-analysis of the literature and report of six cases. Spine (Phila Pa 1976) 22(17):2009–2014 ((Scoliosis in twins 1997. 1; discussion 2015))

    CAS  Article  Google Scholar 

  53. 53.

    Ogura Y, Kou I, Miura S et al (2015) A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am J Human Genet 97(2):337–342

    CAS  Article  Google Scholar 

  54. 54.

    McMaster ME, Lee AJ, Burwell RG (2015) Physical activities of Patients with adolescent idiopathic scoliosis (AIS): preliminary longitudinal case-control study historical evaluation of possible risk factors. Scoliosis 18(10):6

    Article  Google Scholar 

  55. 55.

    Machida M, Dubousset J, Imamura Y et al (1993) An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine (Phila Pa 1976) 18(12):1609–1615

    CAS  Article  Google Scholar 

  56. 56.

    Qiu XS, Tang NL, Yeung HY et al (2007) Genetic association study of growth hormone receptor and idiopathic scoliosis. Clin Orthop Relat Res 462:53–58

    PubMed  Article  Google Scholar 

  57. 57.

    Dretakis EK (2000) Brain-stem dysfunction and idiopathic scoliosis. Stud Health Technol Inform 2002(91):422–427

    Google Scholar 

  58. 58.

    Sina RK, Sandip PT, Woojin C (2019) Etiology of adolescent idiopathic scoliosis: a literature review. Asian Spine J 13(3):519–526

    Article  Google Scholar 

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We would like to acknowledge all laboratory staff at Department of Laboratory LR11ES41 Genetic Biodiversity and Valorization of Bio-resources, 5000, Monastir, Tunisia. for the funding and technical support that we presented and for their encouragement to succeed in this work.


The financemet was provided by Monastir University, Monastir Higher Institute of Biotechnology, Laboratory LR11ES41, Genetics Biodiversity and Valorization of Bio-resources, 5000, Monastir, Tunisia.

Author information




LS: substantial contributions to design of the work; acquisition, analysis, and interpretation of data for the work; and drafting the work and final approval of the version to be published. KK: interpretation of data for the work; and revising it critically for important intellectual content; and final approval of the version to be published. MI: substantial contributions to the conception of the work; and it critically for important intellectual content; and final approval of the version to be published.

Corresponding author

Correspondence to Samar Lahmar.

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The handling and sacrifice of animals have been applied in the regulation of the IRB approval/Research Ethics Committee of the Monastir Higher Institute of Biotechnology, University of Monastir, Tunisia.

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Lahmar, S., Kessabi, K. & Messaoudi, I. Aphanius fasciatus: a molecular model of scoliosis?. Spine Deform (2021). https://doi.org/10.1007/s43390-021-00291-w

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  • Aphanius fasciatus
  • Human idiopathic scoliosis
  • Natural model