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“Out of the Dark” Cavefish Are Entering Biomedical Research

  • Nicolas Rohner
Chapter

Abstract

The emergence of cheaper sequencing platforms and more widely applicable genome editing techniques is empowering new model organisms to emerge in the field of biomedical science. A promising branch of such organisms are the so-called evolutionary mutant models. To be covered by this definition, an animal must display phenotypes reminiscent of human pathologies, but these phenotypes must be part of the animal’s natural condition. In other words, these animals are not considered sick, but rather they have evolved disease-like traits as part of their strategy to survive in the wild. The cavefish Astyanax mexicanus is such an animal species. A. mexicanus displays many traits resembling a variety of human pathologies including retinal degenerations, diabetes-like phenotypes, and even psychiatric diseases. The study of evolutionary mutant models, such as the cavefish, promises to provide important new insights into human pathologies by offering a different perspective compared to the classical model systems. Here, I introduce the cavefish model system Astyanax mexicanus to the reader and provide an overview of the latest efforts to establish this species as a valid member of animal models that are successfully used in biomedical research.

Keywords

Cavefish Astyanax mexicanus Adaptation Evolutionary mutant models Albinism Blindness Asymmetry Autism Sleep loss Circadian rhythm Regeneration Obesity 

References

  1. Albertson RC, Cresko W, Detrich HW 3rd, Postlethwait JH (2009) Evolutionary mutant models for human disease. Trends Genet 25(2):74–81CrossRefPubMedGoogle Scholar
  2. Arnaout R, Reischauer S, Stainier DY (2014) Recovery of adult zebrafish hearts for high-throughput applications. J Vis Exp 94Google Scholar
  3. Aspiras AC, Rohner N, Martineau B, Borowsky RL, Tabin CJ (2015) Melanocortin 4 receptor mutations contribute to the adaptation of cavefish to nutrient-poor conditions. Proc Natl Acad Sci U S A 112(31):9668–9673CrossRefPubMedPubMedCentralGoogle Scholar
  4. Beale A, Guibal C, Tamai TK, Klotz L, Cowen S, Peyric E, Reynoso VH, Yamamoto Y, Whitmore D (2013) Circadian rhythms in Mexican blind cavefish Astyanax mexicanus in the lab and in the field. Nat Commun 4:2769CrossRefPubMedGoogle Scholar
  5. Behrmann-Godel J, Nolte AW, Kreiselmaier J, Berka R, Freyhof J (2017) The first European cave fish. Curr Biol 27(7):R257–R258CrossRefPubMedGoogle Scholar
  6. Bolker J (2012) Model organisms: there’s more to life than rats and flies. Nature 491(7422):31–33CrossRefPubMedGoogle Scholar
  7. Braasch I, Peterson SM, Desvignes T, McCluskey BM, Batzel P, Postlethwait JH (2015) A new model army: emerging fish models to study the genomics of vertebrate Evo-devo. J Exp Zool B Mol Dev Evol 324(4):316–341CrossRefPubMedGoogle Scholar
  8. Bravo-Gil N, Gonzalez-Del Pozo M, Martin-Sanchez M, Mendez-Vidal C, Rodriguez-de la Rua E, Borrego S, Antinolo G (2017) Unravelling the genetic basis of simplex retinitis Pigmentosa cases. Sci Rep 7:41937CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823CrossRefPubMedPubMedCentralGoogle Scholar
  10. Daiger SP, Sullivan LS, Bowne SJ (2013) Genes and mutations causing retinitis pigmentosa. Clin Genet 84(2):132–141CrossRefPubMedGoogle Scholar
  11. Di Palma F, Kidd C, Borowsky R, Kocher TD (2007) Construction of bacterial artificial chromosome libraries for the Lake Malawi cichlid (Metriaclima zebra), and the blind cavefish (Astyanax mexicanus). Zebrafish 4(1):41–47CrossRefPubMedGoogle Scholar
  12. Duboue ER, Keene AC, Borowsky RL (2011) Evolutionary convergence on sleep loss in cavefish populations. Curr Biol 21(8):671–676CrossRefPubMedGoogle Scholar
  13. Duboue ER, Borowsky RL, Keene AC (2012) Beta-adrenergic signaling regulates evolutionarily derived sleep loss in the Mexican cavefish. Brain Behav Evol 80(4):233–243CrossRefPubMedGoogle Scholar
  14. Elipot Y, Legendre L, Pere S, Sohm F, Retaux S (2014) Astyanax transgenesis and husbandry: how cavefish enters the laboratory. Zebrafish 11(4):291–299CrossRefPubMedGoogle Scholar
  15. Fox JG, Barthold SW, Davisson MT (2007) The mouse in biomedical research. Elsevier, Amsterdam. ISBN: 9780123694584Google Scholar
  16. Goldstein B, King N (2016) The future of cell biology: emerging model organisms. Trends Cell Biol 26(11):818–824CrossRefPubMedPubMedCentralGoogle Scholar
  17. Goodwin S, McPherson JD, McCombie WR (2016) Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet 17(6):333–351CrossRefGoogle Scholar
  18. Gravett N, Bhagwandin A, Sutcliffe R, Landen K, Chase MJ, Lyamin OI, Siegel JM, Manger PR (2017) Inactivity/sleep in two wild free-roaming African elephant matriarchs - does large body size make elephants the shortest mammalian sleepers? PLoS One 12(3):e0171903CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gross JB (2012) The complex origin of Astyanax cavefish. BMC Evol Biol 12:105CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gross JB, Protas M, Conrad M, Scheid PE, Vidal O, Jeffery WR, Borowsky R, Tabin CJ (2008) Synteny and candidate gene prediction using an anchored linkage map of Astyanax mexicanus. Proc Natl Acad Sci U S A 105(51):20106–20111CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gross JB, Borowsky R, Tabin CJ (2009) A novel role for Mc1r in the parallel evolution of depigmentation in independent populations of the cavefish Astyanax mexicanus. PLoS Genet 5(1):e1000326CrossRefPubMedPubMedCentralGoogle Scholar
  22. Gross JB, Krutzler AJ, Carlson BM (2014) Complex craniofacial changes in blind cave-dwelling fish are mediated by genetically symmetric and asymmetric loci. Genetics 196(4):1303–1319CrossRefPubMedPubMedCentralGoogle Scholar
  23. Gross JB, Meyer B, Perkins M (2015) The rise of Astyanax cavefish. Dev Dyn 244(9):1031–1038CrossRefPubMedPubMedCentralGoogle Scholar
  24. Gross JB, Gangidine A, Powers AK (2016) Asymmetric facial bone fragmentation mirrors asymmetric distribution of cranial Neuromasts in blind Mexican cavefish, Symmetry (Basel) 8(11)CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gusev A, Lee SH, Trynka G, Finucane H, Vilhjalmsson BJ, Xu H, Zang C, Ripke S, Bulik-Sullivan B, Stahl E, Kahler AK, Hultman CM, Purcell SM, McCarroll SA, Daly M, Pasaniuc B, Sullivan PF, Neale BM, Wray NR, Raychaudhuri S, Price AL (2014) Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am J Hum Genet 95(5):535–552CrossRefPubMedPubMedCentralGoogle Scholar
  26. Hervant F, Malard F (2012) Responses to low oxygen. In: Encyclopedia of caves, Second edn. Academic Press, United Kingdom, pp 651–658. ISBN: 978-0-12-383832-2CrossRefGoogle Scholar
  27. Hubbard JK, Uy JA, Hauber ME, Hoekstra HE, Safran RJ (2010) Vertebrate pigmentation: from underlying genes to adaptive function. Trends Genet 26(5):231–239CrossRefPubMedGoogle Scholar
  28. Itani O, Jike M, Watanabe N, Kaneita Y (2017) Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med 32:246–256CrossRefPubMedGoogle Scholar
  29. Jaggard J, Robinson BG, Stahl BA, Oh I, Masek P, Yoshizawa M, Keene AC (2017) The lateral line confers evolutionarily derived sleep loss in the Mexican cavefish. J Exp Biol 220(Pt 2):284–293CrossRefPubMedGoogle Scholar
  30. Joshua M, Lisberger SG (2015) A tale of two species: neural integration in zebrafish and monkeys. Neuroscience 296:80–91CrossRefPubMedGoogle Scholar
  31. Keene A, Yoshizawa M, McGaugh S (2016) Biology and evolution of the Mexican cavefish. Elsevier Inc, New York. ISBN: 9780128021484CrossRefGoogle Scholar
  32. Krishnan J, Rohner N (2017) Cavefish and the basis for eye loss. Philos Trans R Soc Lond Ser B Biol Sci 372(1713)CrossRefGoogle Scholar
  33. Krogh (1929) The progress of physiology. Am J Phys 90(2):243–251Google Scholar
  34. Lauer M (2016) A look at NIH support for model organisms, NIH office of extramural research – extramural nexus. https://nexus.od.nih.gov/all/2016/08/03/model-organisms-part-two/
  35. Lieberman D (2014) The story of the human body: evolution, health, and disease. First Vintage Books Edition. ISBN: 978-0307741806Google Scholar
  36. Lu YF, Goldstein DB, Angrist M, Cavalleri G (2014) Personalized medicine and human genetic diversity. Cold Spring Harb Perspect Med 4(9):a008581CrossRefPubMedPubMedCentralGoogle Scholar
  37. Ma L, Parkhurst A, Jeffery WR (2014) The role of a lens survival pathway including sox2 and alphaA-crystallin in the evolution of cavefish eye degeneration. EvoDevo 5:28CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ma L, Jeffery WR, Essner JJ, Kowalko JE (2015) Genome editing using TALENs in blind Mexican cavefish, Astyanax mexicanus. PLoS One 10(3):e0119370CrossRefPubMedPubMedCentralGoogle Scholar
  39. Masek P, Reynolds LA, Bollinger WL, Moody C, Mehta A, Murakami K, Yoshizawa M, Gibbs AG, Keene AC (2014) Altered regulation of sleep and feeding contributes to starvation resistance in Drosophila melanogaster. J Exp Biol 217(Pt 17):3122–3132CrossRefPubMedPubMedCentralGoogle Scholar
  40. Massey JH, Wittkopp PJ (2016) The genetic basis of pigmentation differences within and between Drosophila species. Curr Top Dev Biol 119:27–61CrossRefPubMedPubMedCentralGoogle Scholar
  41. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J, Shafer A, Neri F, Lee K, Kutyavin T, Stehling-Sun S, Johnson AK, Canfield TK, Giste E, Diegel M, Bates D, Hansen RS, Neph S, Sabo PJ, Heimfeld S, Raubitschek A, Ziegler S, Cotsapas C, Sotoodehnia N, Glass I, Sunyaev SR, Kaul R, Stamatoyannopoulos JA (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337(6099):1190–1195CrossRefPubMedPubMedCentralGoogle Scholar
  42. McGaugh SE, Gross JB, Aken B, Blin M, Borowsky R, Chalopin D, Hinaux H, Jeffery WR, Keene A, Ma L, Minx P, Murphy D, O’Quin KE, Retaux S, Rohner N, Searle SM, Stahl BA, Tabin C, Volff JN, Yoshizawa M, Warren WC (2014) The cavefish genome reveals candidate genes for eye loss. Nat Commun 5:5307Google Scholar
  43. Mommersteeg T (2015) The blind cavefish: unravelling the mechanisms underlying heart regeneration. In: Noujaim S (ed) Oxford Talks. https://talks.ox.ac.uk/talks/id/bc3fb05d-2e63-448f-a1eb-caa367afa4e1/
  44. Moran D, Softley R, Warrant EJ (2014) Eyeless Mexican cavefish save energy by eliminating the circadian rhythm in metabolism. PLoS One 9(9):e107877CrossRefPubMedPubMedCentralGoogle Scholar
  45. Mullen LM, Vignieri SN, Gore JA, Hoekstra HE (2009) Adaptive basis of geographic variation: genetic, phenotypic and environmental differences among beach mouse populations. Proc Biol Sci 276(1674):3809–3818CrossRefPubMedPubMedCentralGoogle Scholar
  46. O’Quin KE, Yoshizawa M, Doshi P, Jeffery WR (2013) Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus. PLoS One 8(2):e57281CrossRefPubMedPubMedCentralGoogle Scholar
  47. Penney CC, Volkoff H (2014) Peripheral injections of cholecystokinin, apelin, ghrelin and orexin in cavefish (Astyanax fasciatus mexicanus): effects on feeding and on the brain expression levels of tyrosine hydroxylase, mechanistic target of rapamycin and appetite-related hormones. Gen Comp Endocrinol 196:34–40CrossRefPubMedGoogle Scholar
  48. Pennisi E (2016) Antisocial cave fish may hold clues to schizophrenia, autism. Science. (Magazine Health, Plants & Animals). https://doi.org/10.1126/science.aaf5813
  49. Perlman RL (2016) Mouse models of human disease: an evolutionary perspective. Evol Med Public Health 2016(1):170–176PubMedPubMedCentralGoogle Scholar
  50. Powers AK, Davis EM, Kaplan SA, Gross JB (2017) Cranial asymmetry arises later in the life history of the blind Mexican cavefish, Astyanax mexicanus. PLoS One 12(5):e0177419CrossRefPubMedPubMedCentralGoogle Scholar
  51. Protas ME, Hersey C, Kochanek D, Zhou Y, Wilkens H, Jeffery WR, Zon LI, Borowsky R, Tabin CJ (2006) Genetic analysis of cavefish reveals molecular convergence in the evolution of albinism. Nat Genet 38(1):107–111CrossRefPubMedGoogle Scholar
  52. Protas M, Tabansky I, Conrad M, Gross JB, Vidal O, Tabin CJ, Borowsky R (2008) Multi-trait evolution in a cave fish Astyanax mexicanus. Evol Dev 10(2):196–209CrossRefPubMedGoogle Scholar
  53. Rechtschaffen A, Gilliland MA, Bergmann BM, Winter JB (1983) Physiological correlates of prolonged sleep deprivation in rats. Science 221(4606):182–184CrossRefPubMedGoogle Scholar
  54. Reissmann M, Ludwig A (2013) Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals. Semin Cell Dev Biol 24(6–7):576–586CrossRefPubMedGoogle Scholar
  55. Salin K, Voituron Y, Mourin J, Hervant F (2010) Cave colonization without fasting capacities: an example with the fish Astyanax fasciatus mexicanus. Comp Biochem Physiol A Mol Integr Physiol 156(4):451–457CrossRefPubMedGoogle Scholar
  56. Schneider A, Henegar C, Day K, Absher D, Napolitano C, Silveira L, David VA, O’Brien SJ, Menotti-Raymond M, Barsh GS, Eizirik E (2015) Recurrent evolution of melanism in South American felids. PLoS Genet 11(2):e1004892CrossRefPubMedPubMedCentralGoogle Scholar
  57. Stahl BA, Gross JB (2015) Alterations in Mc1r gene expression are associated with regressive pigmentation in Astyanax cavefish. Dev Genes Evol 225(6):367–375CrossRefPubMedPubMedCentralGoogle Scholar
  58. Wall A, Volkoff H (2013) Effects of fasting and feeding on the brain mRNA expressions of orexin, tyrosine hydroxylase (TH), PYY and CCK in the Mexican blind cavefish (Astyanax fasciatus mexicanus). Gen Comp Endocrinol 183:44–52CrossRefPubMedGoogle Scholar
  59. Wray GA (2007) The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 8(3):206–216CrossRefPubMedGoogle Scholar
  60. Wu CW, Biggar KK, Storey KB (2013) Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance. Braz J Med Biol Res 46(1):1–13CrossRefPubMedPubMedCentralGoogle Scholar
  61. Yamamoto Y, Stock DW, Jeffery WR (2004) Hedgehog signalling controls eye degeneration in blind cavefish. Nature 431(7010):844–847CrossRefPubMedGoogle Scholar
  62. Yoshizawa M (2015) Behaviors of cavefish offer insight into developmental evolution. Mol Reprod Dev 82(4):268–280CrossRefPubMedPubMedCentralGoogle Scholar
  63. Yoshizawa M, Robinson BG, Duboue ER, Masek P, Jaggard JB, O’Quin KE, Borowsky RL, Jeffery WR, Keene AC (2015) Distinct genetic architecture underlies the emergence of sleep loss and prey-seeking behavior in the Mexican cavefish. BMC Biol 13:15Google Scholar
  64. Zhang QG (2006) Hypertension and counter-hypertension mechanisms in giraffes. Cardiovasc Hematol Disord Drug Targets 6(1):63–67CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Stowers Institute for Medical ResearchKansas CityUSA
  2. 2.Department of Molecular & Integrative PhysiologyKU Medical CenterKansas CityUSA

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