Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish
Abstract
:1. Introduction
2. Drosophila and Zebrafish Models in Understanding the Molecular Basis of Muscular Diseases
2.1. Drosophila for Disease Modelling and Understanding of Pathogenesis Mechanisms of MD
Disease | Mutated Gene | Animal Model | Mutation Type in Animal Models | Shared Symptoms with Patients | Ref. | ||
---|---|---|---|---|---|---|---|
D | Z | Drosophila | Zebrafish | ||||
DMD/BMD | Dystrophin | ✓ | ✓ | Dys deletion mutants | Nonsense mutation in dystrophin gene | Age-dependent muscle degeneration/Loss of muscle integrity | [33,55] |
Splice mutation in dystrophin gene | [60,61,62] | ||||||
LGMD | Lamin A/C Sarcoglycan Dysferlin POMT1 | ✓ | ✗ | Partial/null mutations in the Drosophila δ-sarcoglycan locus | ✗ | Reduced lifespan & mobility in aged flies | [56] |
DM1 | DMPK | ✓ | ✓ | Expression of CTG repeats in adult/larval muscle | MBNL gene knockdown | Myotonia/Muscle defects Splicing defects Foci formation | [35,36] |
Injection of CUG repeat-containing mRNA | [37,38,68] | ||||||
OPMD | PABPN1 | ✓ | ✗ | Human PABPN1-17ala expressed in adult muscle | ✗ | Progressive muscle degeneration Nuclear inclusions | [57] |
EDMD | Emerin Lamin A/C | ✓ | ✗ | Transgenic flies expressing a mutant form of Lamin-C (lacking the first 42 AA) | ✗ | Muscle defects Early death | [58,59] |
CMD | POMT1 Fukutin Laminin α2 | ✓ | ✓ | Mutants for POMT1 & POMT2 Drosophila orthologs | Point mutation in laminin α2 gene | Shortened lifespan Age-dependent severity of muscle phenotypes/Disorder of primary motor neurons innervation | [39,40] |
2.2. Zebrafish Models Designed to Dissect the Molecular Mechanisms of MD
3. Major Advances for MD through Therapeutic Drug Screening in the Fruitfly and Zebrafish
Disease Model | Animal Model | Type of Performed Screen | Identified Drug/Genetic Modifier Mode of Action | Enhanced/Suppressed Phenotype | Ref. |
---|---|---|---|---|---|
DMD | Drosophila | Genetic interactors of Dys/Dg | Interactors involved in: muscle, motor & cystoskeleton function, neuronal migration or PCP genes, Notch signaling, TGF-β signaling, EGFR signaling | Wing-vein phenotype (anterior and posterior cross veins detached/altered cross veins) | [27,84] |
Reduction of
mbl levels enhance muscle phenotypes Dystrophic flies with reduced wunen exhibit less age-dependent degeneration | Abnormal muscle phenotype | ||||
Zebrafish | Drug screening on sapje and sapje-like mutants | Fluoxetine | Prevention of membrane fragility, survival promotion | [85] | |
Aminophylline, Eprizole, Homochlorcyclizine dihydrochloride, Conessine, Equilin, Pentetic acid, Proscillaridin A, Sildenafil, Crassin acetate, Cerulenin, Prostaglandin | Restoration of normal muscle structure in affected embryos | [86,87,88,89] | |||
Exon-skipping antisense synthetic oligonucleotides (ASO) | Aminoglycoside antibiotics (ataluren-PTC124) | [32,90] | |||
DM1 | Drosophila | Drug screening on DM1 flies(480 interrupted CTG) | 10 suppressor drugs: Non-steroidal anti-inflammatory agents, dopamine receptors and monoamine uptake inhibitors, Na+ and Ca2+ metabolism, Muscarinic, cholinergic and histamine receptors inhibitors, ... | CUG-induced lethality | [91] |
Genetic modifier screening on DM1 flies (480 interrupted CTG) | Suppressors: cnc, Nurf-38, foi, coro, csk, spinster, ... Enhancers: seven up, viking, cg4589 | CUG-induced rough-eye phenotype | |||
Zebrafish | Drug testing on DM1 zebrafish model (CUG-repeat expansion zebrafish model) | Kinase inhibitor (Ro 31-8220) examination - additional assay to complement drug screen performed in cell culture | Partial rescue of somite number and length to width ratio of the tail | [92] |
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Emery, A.E. The muscular dystrophies. Lancet 2002, 359, 687–695. [Google Scholar] [CrossRef]
- Mercuri, E.; Muntoni, F. Muscular dystrophies. Lancet 2013, 381, 845–860. [Google Scholar] [CrossRef]
- Sparrow, J.; Hughes, S.M.; Segalat, L. Other model organisms for sarcomeric muscle diseases. Adv. Exp. Med. Biol. 2008, 642, 192–206. [Google Scholar]
- Rubin, G.M.; Lewis, E.B. A brief history of drosophila’s contributions to genome research. Science 2000, 287, 2216–2218. [Google Scholar] [CrossRef]
- Arias, A.M. Drosophila melanogaster and the development of biology in the 20th century. In Methods in Molecular Biology: Drosophila: Methods and Protocols; Springer: Totowa, NJ, USA, 2008; pp. 1–25. [Google Scholar]
- Adams, M.D.; Celniker, S.E.; Holt, R.A.; Evans, C.A.; Gocayne, J.D.; Amanatides, P.G.; Scherer, S.E.; Li, P.W.; Hoskins, R.A.; Galle, R.F.; et al. The genome sequence of Drosophila melanogaster. Science 2000, 287, 2185–2195. [Google Scholar] [CrossRef] [PubMed]
- Reiter, L.T.; Potocki, L.; Chien, S.; Gribskov, M.; Bier, E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001, 11, 1114–1125. [Google Scholar] [CrossRef]
- Lloyd, T.E.; Taylor, J.P. Flightless flies: Drosophila models of neuromuscular disease. Ann. N. Y. Acad. Sci. 2010, 1184, e1–e20. [Google Scholar] [CrossRef]
- Howe, K.; Clark, M.D.; Torroja, C.F.; Torrance, J.; Berthelot, C.; Muffato, M.; Collins, J.E.; Humphray, S.; McLaren, K.; Matthews, L.; et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 2013, 496, 498–503. [Google Scholar] [CrossRef]
- Barbazuk, W.B.; Korf, I.; Kadavi, C.; Heyen, J.; Tate, S.; Wun, E.; Bedell, J.A.; McPherson, J.D.; Johnson, S.L. The syntenic relationship of the zebrafish and human genomes. Genome Res. 2000, 10, 1351–1358. [Google Scholar] [CrossRef]
- Bedell, V.M.; Westcot, S.E.; Ekker, S.C. Lessons from morpholino-based screening in zebrafish. Brief. Funct. Genomics 2011, 10, 181–188. [Google Scholar] [CrossRef]
- Stainier, D.Y.R.; Kontarakis, Z.; Rossi, A. Making sense of anti-sense data. Dev. Cell 2015, 32, 7–8. [Google Scholar] [CrossRef]
- Granato, M.; van Eeden, F.J.; Schach, U.; Trowe, T.; Brand, M.; Furutani-Seiki, M.; Haffter, P.; Hammerschmidt, M.; Heisenberg, C.P.; Jiang, Y.J.; et al. Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva. Dev. Camb. Engl. 1996, 123, 399–413. [Google Scholar]
- Gupta, V.; Kawahara, G.; Gundry, S.R.; Chen, A.T.; Lencer, W.I.; Zhou, Y.; Zon, L.I.; Kunkel, L.M.; Beggs, A.H. The zebrafish dag1 mutant: A novel genetic model for dystroglycanopathies. Hum. Mol. Genet. 2011, 20, 1712–1725. [Google Scholar] [CrossRef]
- Gupta, V.A.; Kawahara, G.; Myers, J.A.; Chen, A.T.; Hall, T.E.; Manzini, M.C.; Currie, P.D.; Zhou, Y.; Zon, L.I.; Kunkel, L.M.; et al. A splice site mutation in laminin-α2 results in a severe muscular dystrophy and growth abnormalities in zebrafish. PLoS ONE 2012, 7, e43794. [Google Scholar] [CrossRef]
- Hirata, H.; Wen, H.; Kawakami, Y.; Naganawa, Y.; Ogino, K.; Yamada, K.; Saint-Amant, L.; Low, S.E.; Cui, W.W.; Zhou, W.; et al. Connexin 39.9 protein is necessary for coordinated activation of slow-twitch muscle and normal behavior in zebrafish. J. Biol. Chem. 2012, 287, 1080–1089. [Google Scholar] [CrossRef] [PubMed]
- Saint-Amant, L.; Sprague, S.M.; Hirata, H.; Li, Q.; Cui, W.W.; Zhou, W.; Poudou, O.; Hume, R.I.; Kuwada, J.Y. The zebrafish ennui behavioral mutation disrupts acetylcholine receptor localization and motor axon stability. Dev. Neurobiol. 2008, 68, 45–61. [Google Scholar] [CrossRef] [PubMed]
- Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J.A.; Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012, 337, 816–821. [Google Scholar] [CrossRef] [PubMed]
- Irion, U.; Krauss, J.; Nusslein-Volhard, C. Precise and efficient genome editing in zebrafish using the CRISPR/Cas9 system. Development 2014, 4827–4830. [Google Scholar] [CrossRef]
- Hruscha, A.; Schmid, B. Generation of zebrafish models by CRISPR/Cas9 genome editing. In Neuronal Cell Death; Lossi, L., Merighi, A., Eds.; Methods in Molecular Biology; Springer: New York, NY, USA, 2015; Series Volume 1254, pp. 341–350. [Google Scholar]
- Bassett, A.R.; Tibbit, C.; Ponting, C.P.; Liu, J.-L. Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep. 2013, 4, 220–228. [Google Scholar] [CrossRef] [PubMed]
- Harrison, M.M.; Jenkins, B.V.; O’Connor-Giles, K.M.; Wildonger, J. A CRISPR view of development. Genes Dev. 2014, 28, 1859–1872. [Google Scholar] [CrossRef]
- Sink, H. Muscle Development in Drosophila; Springer Science & Business Media: New York, NY, USA, 2007. [Google Scholar]
- Baylies, M.K.; Bate, M.; Gomez, M.R. Myogenesis: A view from Drosophila. Cell 1998, 93, 921–927. [Google Scholar] [CrossRef] [PubMed]
- Saint-Amant, L.; Drapeau, P. Time course of the development of motor behaviors in the zebrafish embryo. J. Neurobiol. 1998, 37, 622–632. [Google Scholar] [CrossRef] [PubMed]
- Pandey, U.B.; Nichols, C.D. Human disease models in drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol. Rev. 2011, 63, 411–436. [Google Scholar] [CrossRef] [PubMed]
- Pantoja, M.; Fischer, K.A.; Ieronimakis, N.; Reyes, M.; Ruohola-Baker, H. Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila. Development 2013, 140, 136–146. [Google Scholar] [CrossRef] [PubMed]
- Vaquer, G.; Dannerstedt, F.R.; Mavris, M.; Bignami, F.; Llinares-Garcia, J.; Westermark, K.; Sepodes, B. Animal models for metabolic, neuromuscular and ophthalmological rare diseases. Nat. Rev. Drug Discov. 2013, 12, 287–305. [Google Scholar] [CrossRef] [PubMed]
- Lieschke, G.J.; Currie, P.D. Animal models of human disease: Zebrafish swim into view. Nat. Rev. Genet. 2007, 8, 353–367. [Google Scholar] [CrossRef] [PubMed]
- Maves, L. Recent advances using zebrafish animal models for muscle disease drug discovery. Expert Opin. Drug Discov. 2014, 9, 1033–1045. [Google Scholar] [CrossRef] [PubMed]
- Santoriello, C.; Zon, L.I. Hooked! Modeling human disease in zebrafish. J. Clin. Investig. 2012, 122, 2337–2343. [Google Scholar] [CrossRef] [PubMed]
- Gibbs, E.M.; Horstick, E.J.; Dowling, J.J. Swimming into prominence: The zebrafish as a valuable tool for studying human myopathies and muscular dystrophies. FEBS J. 2013, 280, 4187–4197. [Google Scholar] [CrossRef] [PubMed]
- Shcherbata, H.R.; Yatsenko, A.S.; Patterson, L.; Sood, V.D.; Nudel, U.; Yaffe, D.; Baker, D.; Ruohola-Baker, H. Dissecting muscle and neuronal disorders in a Drosophila model of muscular dystrophy. EMBO J. 2007, 26, 481–493. [Google Scholar] [CrossRef] [PubMed]
- Chambers, S.P.; Dodd, A.; Overall, R.; Sirey, T.; Lam, L.T.; Morris, G.E.; Love, D.R. Dystrophin in adult zebrafish muscle. Biochem. Biophys. Res. Commun. 2001, 286, 478–483. [Google Scholar] [CrossRef] [PubMed]
- De Haro, M.; Al-Ramahi, I.; de Gouyon, B.; Ukani, L.; Rosa, A.; Faustino, N.A.; Ashizawa, T.; Cooper, T.A.; Botas, J. MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1. Hum. Mol. Genet. 2006, 15, 2138–2145. [Google Scholar] [CrossRef] [PubMed]
- Picchio, L.; Plantie, E.; Renaud, Y.; Poovthumkadavil, P.; Jagla, K. Novel Drosophila model of myotonic dystrophy type 1: Phenotypic characterization and genome-wide view of altered gene expression. Hum. Mol. Genet. 2013, 22, 2795–2810. [Google Scholar] [CrossRef] [PubMed]
- Machuca-Tzili, L.E.; Buxton, S.; Thorpe, A.; Timson, C.M.; Wigmore, P.; Luther, P.K.; Brook, J.D. Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy. Dis. Model. Mech. 2011, 4, 381–392. [Google Scholar] [CrossRef] [PubMed]
- Todd, P.K.; Ackall, F.Y.; Hur, J.; Sharma, K.; Paulson, H.L.; Dowling, J.J. Transcriptional changes and developmental abnormalities in a zebrafish model of myotonic dystrophy type 1. Dis. Model. Mech. 2014, 7, 143–155. [Google Scholar] [CrossRef] [PubMed]
- Ueyama, M.; Akimoto, Y.; Ichimiya, T.; Ueda, R.; Kawakami, H.; Aigaki, T.; Nishihara, S. Increased apoptosis of myoblasts in drosophila model for the walker-warburg syndrome. PLoS ONE 2010, 5, e11557. [Google Scholar] [CrossRef] [PubMed]
- Hall, T.E.; Bryson-Richardson, R.J.; Berger, S.; Jacoby, A.S.; Cole, N.J.; Hollway, G.E.; Berger, J.; Currie, P.D. The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin alpha2-deficient congenital muscular dystrophy. Proc. Natl. Acad. Sci. USA 2007, 104, 7092–7097. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, K.F.; Kunkel, L.M. Dystrophin and muscular dystrophy: Past, present, and future. Mol. Genet. Metab. 2001, 74, 75–88. [Google Scholar] [CrossRef] [PubMed]
- Guyon, J.R.; Steffen, L.S.; Howell, M.H.; Pusack, T.J.; Lawrence, C.; Kunkel, L.M. Modeling human muscle disease in zebrafish. Biochim. Biophys. Acta 2007, 1772, 205–215. [Google Scholar] [CrossRef] [PubMed]
- Roberts, R.G.; Bobrow, M. Dystrophins in vertebrates and invertebrates. Hum. Mol. Genet. 1998, 7, 589–595. [Google Scholar] [CrossRef] [PubMed]
- Brook, J.D.; McCurrach, M.E.; Harley, H.G.; Buckler, A.J.; Church, D.; Aburatani, H.; Hunter, K.; Stanton, V.P.; Thirion, J.P.; Hudson, T.; et al. Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell 1992, 69, 385. [Google Scholar] [PubMed]
- Day, J.W.; Ranum, L.P.W. Genetics and molecular pathogenesis of the myotonic dystrophies. Curr. Neurol. Neurosci. Rep. 2005, 5, 55–59. [Google Scholar] [CrossRef] [PubMed]
- Klein, A.F.; Gasnier, E.; Furling, D. Gain of RNA function in pathological cases: Focus on myotonic dystrophy. Biochimie 2011, 93, 2006–2012. [Google Scholar] [CrossRef] [PubMed]
- Meola, G.; Cardani, R. Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim. Biophys. Acta BBA—Mol. Basis Dis. 2015, 1852, 594–606. [Google Scholar] [CrossRef]
- Pettersson, O.J.; Aagaard, L.; Jensen, T.G.; Damgaard, C.K. Molecular mechanisms in DM1—A focus on foci. Nucleic Acids Res. 2015, 43, 2433–2441. [Google Scholar] [CrossRef] [PubMed]
- Bertini, E.; D’Amico, A.; Gualandi, F.; Petrini, S. Congenital muscular dystrophies: A Brief Review. Semin. Pediatr. Neurol. 2011, 18, 277–288. [Google Scholar] [CrossRef] [PubMed]
- Mercuri, E.; Muntoni, F. The ever-expanding spectrum of congenital muscular dystrophies. Ann. Neurol. 2012, 72, 9–17. [Google Scholar] [CrossRef] [PubMed]
- Sparks, S.; Quijano-Roy, S.; Harper, A.; Rutkowski, A.; Gordon, E.; Hoffman, E.P.; Pegoraro, E. Congenital muscular dystrophy overview. In GeneReviews(®); Pagon, R.A., Adam, M.P., Ardinger, H.H., Bird, T.D., Dolan, C.R., Fong, C.-T., Smith, R.J., Stephens, K., Eds.; University of Washington: Seattle, WA, USA, 1993. [Google Scholar]
- Kirschner, J. Congenital muscular dystrophies. In Handbook of Clinical Neurology; Dulac, O., Lassonde, M., Sarnat, H., Eds.; Pediatric Neurology Part III; Elsevier: Amsterdam, The Netherlands, 2013; Volume 113, Chapter 143; pp. 1377–1385. [Google Scholar]
- Dobyns, W.B.; Pagon, R.A.; Armstrong, D.; Curry, C.J.; Greenberg, F.; Grix, A.; Holmes, L.B.; Laxova, R.; Michels, V.V.; Robinow, M. Diagnostic criteria for walker-warburg syndrome. Am. J. Med. Genet. 1989, 32, 195–210. [Google Scholar] [CrossRef] [PubMed]
- Vajsar, J.; Schachter, H. Walker-Warburg syndrome. Orphanet J. Rare Dis. 2006, 1, 29. [Google Scholar] [CrossRef] [PubMed]
- Mosqueira, M.; Willmann, G.; Ruohola-Baker, H.; Khurana, T.S. Chronic hypoxia impairs muscle function in the Drosophila model of Duchenne’s muscular dystrophy (DMD). PLoS ONE 2010, 5, e13450. [Google Scholar] [CrossRef] [PubMed]
- Allikian, M.J.; Bhabha, G.; Dospoy, P.; Heydemann, A.; Ryder, P.; Earley, J.U.; Wolf, M.J.; Rockman, H.A.; McNally, E.M. Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants. Hum. Mol. Genet. 2007, 16, 2933–2943. [Google Scholar] [CrossRef] [PubMed]
- Chartier, A.; Benoit, B.; Simonelig, M. A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic toxicity of PABPN1. EMBO J. 2006, 25, 2253–2262. [Google Scholar] [CrossRef] [PubMed]
- Dialynas, G.; Speese, S.; Budnik, V.; Geyer, P.K.; Wallrath, L.L. The role of Drosophila Lamin C in muscle function and gene expression. Dev. Camb. Engl. 2010, 137, 3067–3077. [Google Scholar]
- Uchino, R.; Nonaka, Y.; Horigome, T.; Sugiyama, S.; Furukawa, K. Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects. Dev. Biol. 2013, 373, 216–227. [Google Scholar] [CrossRef] [PubMed]
- Guyon, J.R.; Goswami, J.; Jun, S.J.; Thorne, M.; Howell, M.; Pusack, T.; Kawahara, G.; Steffen, L.S.; Galdzicki, M.; Kunkel, L.M. Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin. Hum. Mol. Genet. 2009, 18, 202–211. [Google Scholar] [CrossRef] [PubMed]
- Bassett, D.I.; Currie, P.D. The zebrafish as a model for muscular dystrophy and congenital myopathy. Hum. Mol. Genet. 2003, 12, Spec No 2. R265–R270. [Google Scholar] [CrossRef] [PubMed]
- Bassett, D.; Currie, P.D. Identification of a zebrafish model of muscular dystrophy. Clin. Exp. Pharmacol. Physiol. 2004, 31, 537–540. [Google Scholar] [CrossRef] [PubMed]
- Berger, J.; Currie, P.D. Zebrafish models flex their muscles to shed light on muscular dystrophies. Dis. Model. Mech. 2012, 5, 726–732. [Google Scholar] [CrossRef] [PubMed]
- Takeyama, K.; Ito, S.; Yamamoto, A.; Tanimoto, H.; Furutani, T.; Kanuka, H.; Miura, M.; Tabata, T.; Kato, S. Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila. Neuron 2002, 35, 855–864. [Google Scholar] [CrossRef] [PubMed]
- Chan, Y.B.; Miguel-Aliaga, I.; Franks, C.; Thomas, N.; Trülzsch, B.; Sattelle, D.B.; Davies, K.E.; van den Heuvel, M. Neuromuscular defects in a Drosophila survival motor neuron gene mutant. Hum. Mol. Genet. 2003, 12, 1367–1376. [Google Scholar] [CrossRef] [PubMed]
- Chang, S.; Bray, S.M.; Li, Z.; Zarnescu, D.C.; He, C.; Jin, P.; Warren, S.T. Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat. Chem. Biol. 2008, 4, 256–263. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; Condell, M.; Plesken, H.; Edelman-Novemsky, I.; Ma, J.; Ren, M.; Schlame, M. A drosophila model of barth syndrome. Proc. Natl. Acad. Sci. USA 2006, 103, 11584–11588. [Google Scholar] [CrossRef] [PubMed]
- deLorimier, E.; Coonrod, L.A.; Copperman, J.; Taber, A.; Reister, E.E.; Sharma, K.; Todd, P.K.; Guenza, M.G.; Berglund, J.A. Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model. Nucleic Acids Res. 2014, 42, 12768–12778. [Google Scholar] [CrossRef] [PubMed]
- Greener, M.J.; Roberts, R.G. Conservation of components of the dystrophin complex in Drosophila1. FEBS Lett. 2000, 482, 13–18. [Google Scholar] [CrossRef] [PubMed]
- Taghli-Lamallem, O.; Akasaka, T.; Hogg, G.; Nudel, U.; Yaffe, D.; Chamberlain, J.S.; Ocorr, K.; Bodmer, R. Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype. Aging Cell 2008, 7, 237–249. [Google Scholar] [CrossRef] [PubMed]
- Farkas, G.A.; Mccormick, K.M.; Gosselin, L.E. Episodic hypoxia exacerbates respiratory muscle dysfunction in DMDmdx mice. Muscle Nerve 2007, 36, 708–710. [Google Scholar] [CrossRef] [PubMed]
- Houseley, J.M.; Wang, Z.; Brock, G.J.R.; Soloway, J.; Artero, R.; Perez-Alonso, M.; O’Dell, K.M.C.; Monckton, D.G. Myotonic dystrophy associated expanded CUG repeat muscleblind positive ribonuclear foci are not toxic to Drosophila. Hum. Mol. Genet. 2005, 14, 873–883. [Google Scholar] [CrossRef] [PubMed]
- Wairkar, Y.P.; Fradkin, L.G.; Noordermeer, J.N.; DiAntonio, A. Synaptic defects in a drosophila model of congenital muscular dystrophy. J. Neurosci. 2008, 28, 3781–3789. [Google Scholar] [CrossRef] [PubMed]
- Bulfield, G.; Siller, W.G.; Wight, P.A.; Moore, K.J. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc. Natl. Acad. Sci. USA 1984, 81, 1189–1192. [Google Scholar] [CrossRef] [PubMed]
- Sicinski, P.; Geng, Y.; Ryder-Cook, A.S.; Barnard, E.A.; Darlison, M.G.; Barnard, P.J. The molecular basis of muscular dystrophy in the mdx mouse: A point mutation. Science 1989, 244, 1578–1580. [Google Scholar] [CrossRef] [PubMed]
- Im, W.B.; Phelps, S.F.; Copen, E.H.; Adams, E.G.; Slightom, J.L.; Chamberlain, J.S. Differential expression of dystrophin isoforms in strains of mdx mice with different mutations. Hum. Mol. Genet. 1996, 5, 1149–1153. [Google Scholar] [CrossRef] [PubMed]
- Bassett, D.I.; Bryson-Richardson, R.J.; Daggett, D.F.; Gautier, P.; Keenan, D.G.; Currie, P.D. Dystrophin is required for the formation of stable muscle attachments in the zebrafish embryo. Dev. Camb. Engl. 2003, 130, 5851–5860. [Google Scholar]
- Guyon, J.R.; Mosley, A.N.; Zhou, Y.; O’Brien, K.F.; Sheng, X.; Chiang, K.; Davidson, A.J.; Volinski, J.M.; Zon, L.I.; Kunkel, L.M. The dystrophin associated protein complex in zebrafish. Hum. Mol. Genet. 2003, 12, 601–615. [Google Scholar] [CrossRef] [PubMed]
- Kunkel, L.M.; Bachrach, E.; Bennett, R.R.; Guyon, J.; Steffen, L. Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice, and zebrafish. J. Hum. Genet. 2006, 51, 397–406. [Google Scholar] [CrossRef] [PubMed]
- Deconinck, A.E.; Rafael, J.A.; Skinner, J.A.; Brown, S.C.; Potter, A.C.; Metzinger, L.; Watt, D.J.; Dickson, J.G.; Tinsley, J.M.; Davies, K.E. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 1997, 90, 717–727. [Google Scholar] [CrossRef] [PubMed]
- Grady, R.M.; Teng, H.; Nichol, M.C.; Cunningham, J.C.; Wilkinson, R.S.; Sanes, J.R. Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: A model for Duchenne muscular dystrophy. Cell 1997, 90, 729–738. [Google Scholar] [CrossRef] [PubMed]
- Collins, C.A.; Morgan, J.E. Duchenne’s muscular dystrophy: Animal models used to investigate pathogenesis and develop therapeutic strategies. Int. J. Exp. Pathol. 2003, 84, 165–172. [Google Scholar] [CrossRef] [PubMed]
- Jones, K.J.; Morgan, G.; Johnston, H.; Tobias, V.; Ouvrier, R.A.; Wilkinson, I.; North, K.N. The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case series and review. J. Med. Genet. 2001, 38, 649–657. [Google Scholar] [CrossRef] [PubMed]
- Kucherenko, M.M.; Pantoja, M.; Yatsenko, A.S.; Shcherbata, H.R.; Fischer, K.A.; Maksymiv, D.V.; Chernyk, Y.I.; Ruohola-Baker, H. Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex. PLoS ONE 2008, 3, e2418. [Google Scholar] [CrossRef] [PubMed]
- Waugh, T.A.; Horstick, E.; Hur, J.; Jackson, S.W.; Davidson, A.E.; Li, X.; Dowling, J.J. Fluoxetine prevents dystrophic changes in a zebrafish model of Duchenne muscular dystrophy. Hum. Mol. Genet. 2014, 23, 4651–4662. [Google Scholar] [CrossRef] [PubMed]
- Kawahara, G.; Kunkel, L.M. Zebrafish based small molecule screens for novel DMD drugs. Drug Discov. Today Technol. 2013, 10, e91–e96. [Google Scholar] [CrossRef] [PubMed]
- Kawahara, G.; Karpf, J.A.; Myers, J.A.; Alexander, M.S.; Guyon, J.R.; Kunkel, L.M. Drug screening in a zebrafish model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. USA 2011, 108, 5331–5336. [Google Scholar] [CrossRef] [PubMed]
- Kawahara, G.; Gasperini, M.J.; Myers, J.A.; Widrick, J.J.; Eran, A.; Serafini, P.R.; Alexander, M.S.; Pletcher, M.T.; Morris, C.A.; Kunkel, L.M. Dystrophic muscle improvement in zebrafish via increased heme oxygenase signaling. Hum. Mol. Genet. 2014, 23, 1869–1878. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Andersson-Lendahl, M.; Sejersen, T.; Arner, A. Muscle dysfunction and structural defects of dystrophin-null sapje mutant zebrafish larvae are rescued by ataluren treatment. FASEB J. 2014, 28, 1593–1599. [Google Scholar] [CrossRef] [PubMed]
- Berger, J.; Berger, S.; Jacoby, A.S.; Wilton, S.D.; Currie, P.D. Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish. J. Cell. Mol. Med. 2011, 15, 2643–2651. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Lopez, A.; Monferrer, L.; Garcia-Alcover, I.; Vicente-Crespo, M.; Alvarez-Abril, M.C.; Artero, R.D. Genetic and chemical modifiers of a CUG toxicity Model in drosophila. PLoS ONE 2008, 3, e1595. [Google Scholar] [CrossRef] [PubMed]
- Ketley, A.; Chen, C.Z.; Li, X.; Arya, S.; Robinson, T.E.; Granados-Riveron, J.; Udosen, I.; Morris, G.E.; Holt, I.; Furling, D.; et al. High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines. Hum. Mol. Genet. 2014, 23, 1551–1562. [Google Scholar] [CrossRef] [PubMed]
- Blau, H.M.; Springer, M.L. Gene therapy—A novel Form of Drug Delivery. N. Engl. J. Med. 1995, 333, 1204–1207. [Google Scholar] [CrossRef] [PubMed]
- Chamberlain, J.S. Gene therapy of muscular dystrophy. Hum. Mol. Genet. 2002, 11, 2355–2362. [Google Scholar] [CrossRef] [PubMed]
- Malik, V.; Rodino-Klapac, L.R.; Mendell, J.R. Emerging drugs for Duchenne muscular dystrophy. Expert Opin. Emerg. Drugs 2012, 17, 261–277. [Google Scholar] [CrossRef] [PubMed]
- Benedetti, S.; Hoshiya, H.; Tedesco, F.S. Repair or replace? Exploiting novel gene and cell therapy strategies for muscular dystrophies. FEBS J. 2013, 280, 4263–4280. [Google Scholar] [CrossRef] [PubMed]
- Giacomotto, J.; Ségalat, L. High-throughput screening and small animal models, where are we. Br. J. Pharmacol. 2010, 160, 204–216. [Google Scholar] [CrossRef] [PubMed]
- McKoy, A.F.; Chen, J.; Schupbach, T.; Hecht, M.H. A novel inhibitor of Amyloid β (Aβ) peptide aggregation from high throughput screening to efficacy in an animal model of alzheimer disease. J. Biol. Chem. 2012, 287, 38992–39000. [Google Scholar] [CrossRef] [PubMed]
- Qurashi, A.; Liu, H.; Ray, L.; Nelson, D.L.; Duan, R.; Jin, P. Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila. Hum. Mol. Genet. 2012, 21, 2068–2075. [Google Scholar] [CrossRef] [PubMed]
- Schulte, J.; Sepp, K.J.; Wu, C.; Hong, P.; Littleton, J.T. High-content chemical and RNAi screens for suppressors of neurotoxicity in a huntington’s disease model. PLoS ONE 2011, 6, e23841. [Google Scholar] [CrossRef] [PubMed][Green Version]
- García-López, A.; Llamusí, B.; Orzáez, M.; Pérez-Payá, E.; Artero, R.D. In vivo discovery of a peptide that prevents CUG–RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models. Proc. Natl. Acad. Sci. USA 2011, 108, 11866–11871. [Google Scholar] [CrossRef] [PubMed][Green Version]
- St Johnston, D. The art and design of genetic screens: drosophila melanogaster. Nat. Rev. Genet. 2002, 3, 176–188. [Google Scholar] [CrossRef] [PubMed]
- Chang, H.C.-H.; Dimlich, D.N.; Yokokura, T.; Mukherjee, A.; Kankel, M.W.; Sen, A.; Sridhar, V.; Fulga, T.A.; Hart, A.C.; Van Vactor, D.; et al. Modeling spinal muscular atrophy in Drosophila. PLoS ONE 2008, 3, e3209. [Google Scholar] [CrossRef] [PubMed]
- Ritson, G.P.; Custer, S.K.; Freibaum, B.D.; Guinto, J.B.; Geffel, D.; Moore, J.; Tang, W.; Winton, M.J.; Neumann, M.; Trojanowski, J.Q.; et al. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J. Neurosci. 2010, 30, 7729–7739. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kucherenko, M.M.; Marrone, A.K.; Rishko, V.M.; Magliarelli Hde, F.; Shcherbata, H.R. Stress and muscular dystrophy: A genetic screen for Dystroglycan and Dystrophin interactors in Drosophila identifies cellular stress response components. Dev. Biol. 2011, 352, 228–242. [Google Scholar] [CrossRef] [PubMed]
- De Haro, M.; Al-Ramahi, I.; Jones, K.R.; Holth, J.K.; Timchenko, L.T.; Botas, J. Smaug/SAMD4A restores translational activity of CUGBP1 and suppresses CUG-Induced myopathy. PLoS Genet 2013, 9, e1003445. [Google Scholar] [CrossRef] [PubMed]
- Phillips, J.B.; Westerfield, M. Zebrafish models in translational research: Tipping the scales toward advancements in human health. Dis. Model. Mech. 2014, 7, 739–743. [Google Scholar] [CrossRef] [PubMed]
© 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Plantié, E.; Migocka-Patrzałek, M.; Daczewska, M.; Jagla, K. Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish. Molecules 2015, 20, 6237-6253. https://doi.org/10.3390/molecules20046237
Plantié E, Migocka-Patrzałek M, Daczewska M, Jagla K. Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish. Molecules. 2015; 20(4):6237-6253. https://doi.org/10.3390/molecules20046237
Chicago/Turabian StylePlantié, Emilie, Marta Migocka-Patrzałek, Małgorzata Daczewska, and Krzysztof Jagla. 2015. "Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish" Molecules 20, no. 4: 6237-6253. https://doi.org/10.3390/molecules20046237