Abstract
In the last years, the field of inheritable ventricular arrhythmia disease modelling has changed significantly with a push towards the use of novel cellular cardiomyocyte based models. However, there is a growing need for new in vivo models to study the disease pathology at the tissue and organ level. Zebrafish provide an excellent opportunity for in vivo modelling of inheritable ventricular arrhythmia syndromes due to the remarkable similarity between their cardiac electrophysiology and that of humans. Additionally, many state-of-the-art methods in gene editing and electrophysiological phenotyping are available for zebrafish research. In this review, we give a comprehensive overview of the published zebrafish genetic models for primary electrical disorders and arrhythmogenic cardiomyopathy. We summarise and discuss the strengths and weaknesses of the different technical approaches for the generation of genetically modified zebrafish disease models, as well as the electrophysiological approaches in zebrafish phenotyping. By providing this detailed overview, we aim to draw attention to the potential of the zebrafish model for studying arrhythmia syndromes at the organ level and as a platform for personalised medicine and drug testing.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abramochkin DV, Hassinen M, Vornanen M (2018) Transcripts of Kv7.1 and MinK channels and slow delayed rectifier K(+) current (IKs) are expressed in zebrafish (Danio rerio) heart. Pflugers Arch 470(12):1753–1764. https://doi.org/10.1007/s00424-018-2193-1
Adler A, Novelli V, Amin AS, Abiusi E, Care M, Nannenberg EA et al (2020) An international, multicentered, evidence-based reappraisal of genes reported to cause congenital long QT syndrome. Circulation 141(6):418–428. https://doi.org/10.1161/CIRCULATIONAHA.119.043132
Adli M (2018) The CRISPR tool kit for genome editing and beyond. Nat Commun 9(1):1911. https://doi.org/10.1038/s41467-018-04252-2
Albadri S, De Santis F, Di Donato V, Del Bene F (2017) CRISPR/Cas9-mediated knockin and knockout in zebrafish. In: Jaenisch R, Zhang F, Gage F (eds) Genome editing in neurosciences. Springer, Cham, pp 41–49
Alday A, Alonso H, Gallego M, Urrutia J, Letamendia A, Callol C et al (2014) Ionic channels underlying the ventricular action potential in zebrafish embryo. Pharmacol Res 84:26–31. https://doi.org/10.1016/j.phrs.2014.03.011
Arnaout R, Ferrer T, Huisken J, Spitzer K, Stainier DY, Tristani-Firouzi M et al (2007) Zebrafish model for human long QT syndrome. Proc Natl Acad Sci U S A 104(27):11316–11321. https://doi.org/10.1073/pnas.0702724104
Asimaki A, Kapoor S, Plovie E, Karin Arndt A, Adams E, Liu Z et al (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Transl Med 6(240):240ra74. https://doi.org/10.1126/scitranslmed.3008008
Baker K, Warren KS, Yellen G, Fishman MC (1997) Defective “pacemaker” current (Ih) in a zebrafish mutant with a slow heart rate. Proc Natl Acad Sci U S A 94(9):4554–4559. https://doi.org/10.1073/pnas.94.9.4554
Berchtold MW, Zacharias T, Kulej K, Wang K, Torggler R, Jespersen T et al (2016) The arrhythmogenic calmodulin mutation D129G dysregulates cell growth, calmodulin-dependent kinase II activity, and cardiac function in zebrafish. J Biol Chem 291(52):26636–26646. https://doi.org/10.1074/jbc.M116.758680
Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F et al (2013) Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nat Genet 45(9):1044–1049. https://doi.org/10.1038/ng.2712
Bezzina CR, Lahrouchi N, Priori SG (2015) Genetics of sudden cardiac death. Circ Res 116(12):1919–1936. https://doi.org/10.1161/CIRCRESAHA.116.304030
Bill BR, Petzold AM, Clark KJ, Schimmenti LA, Ekker SC (2009) A primer for morpholino use in zebrafish. Zebrafish 6(1):69–77. https://doi.org/10.1089/zeb.2008.0555
Boel A, De Saffel H, Steyaert W, Callewaert B, De Paepe A, Coucke PJ et al (2018) CRISPR/Cas9-mediated homology-directed repair by ssODNs in zebrafish induces complex mutational patterns resulting from genomic integration of repair-template fragments. Dis Model Mech 11(10). https://doi.org/10.1242/dmm.035352
Bovo E, Dvornikov AV, Mazurek SR, de Tombe PP, Zima AV (2013) Mechanisms of Ca(2)+ handling in zebrafish ventricular myocytes. Pflugers Arch 465(12):1775–1784. https://doi.org/10.1007/s00424-013-1312-2
Brette F, Luxan G, Cros C, Dixey H, Wilson C, Shiels HA (2008) Characterization of isolated ventricular myocytes from adult zebrafish (Danio rerio). Biochem Biophys Res Commun 374(1):143–146. https://doi.org/10.1016/j.bbrc.2008.06.109
Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T et al (2019) Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Transl Res 208:15–29. https://doi.org/10.1016/j.trsl.2019.02.004
Campuzano O, Sarquella-Brugada G, Cesar S, Arbelo E, Brugada J, Brugada R (2018) Recent advances in short QT syndrome. Front Cardiovasc Med 5:149. https://doi.org/10.3389/fcvm.2018.00149
Cerrone M, Remme CA, Tadros R, Bezzina CR, Delmar M (2019) Beyond the one gene-one disease paradigm: complex genetics and pleiotropy in inheritable cardiac disorders. Circulation 140(7):595–610. https://doi.org/10.1161/CIRCULATIONAHA.118.035954
Chablais F, Veit J, Rainer G, Jazwinska A (2011) The zebrafish heart regenerates after cryoinjury-induced myocardial infarction. BMC Dev Biol 11:21. https://doi.org/10.1186/1471-213X-11-21
Chelko SP, Asimaki A, Andersen P, Bedja D, Amat-Alarcon N, DeMazumder D et al (2016) Central role for GSK3beta in the pathogenesis of arrhythmogenic cardiomyopathy. JCI Insight 1(5). https://doi.org/10.1172/jci.insight.85923
Chernyavskaya Y, Ebert AM, Milligan E, Garrity DM (2012) Voltage-gated calcium channel CACNB2 (beta2.1) protein is required in the heart for control of cell proliferation and heart tube integrity. Dev Dyn 241(4):648–662. https://doi.org/10.1002/dvdy.23746
Chi NC, Shaw RM, Jungblut B, Huisken J, Ferrer T, Arnaout R et al (2008) Genetic and physiologic dissection of the vertebrate cardiac conduction system. PLoS Biol 6(5):e109. https://doi.org/10.1371/journal.pbio.0060109
Chopra SS, Stroud DM, Watanabe H, Bennett JS, Burns CG, Wells KS et al (2010) Voltage-gated sodium channels are required for heart development in zebrafish. Circ Res 106(8):1342–1350. https://doi.org/10.1161/CIRCRESAHA.109.213132
Da'as SI, Thanassoulas A, Calver BL, Beck K, Salem R, Saleh A et al (2019) Arrhythmogenic calmodulin E105A mutation alters cardiac RyR2 regulation leading to cardiac dysfunction in zebrafish. Ann N Y Acad Sci 1448(1):19–29. https://doi.org/10.1111/nyas.14033
de Roos AD, van Zoelen EJ, Theuvenet AP (1996) Determination of gap junctional intercellular communication by capacitance measurements. Pflugers Arch 431(4):556–563. https://doi.org/10.1007/BF02191903
Eisen JS, Smith JC (2008) Controlling morpholino experiments: don’t stop making antisense. Development 135(10):1735–1743. https://doi.org/10.1242/dev.001115
El-Brolosy MA, Kontarakis Z, Rossi A, Kuenne C, Gunther S, Fukuda N et al (2019) Genetic compensation triggered by mutant mRNA degradation. Nature 568(7751):193–197. https://doi.org/10.1038/s41586-019-1064-z
Ficker E, Obejero-Paz CA, Zhao S, Brown AM (2002) The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations. J Biol Chem 277(7):4989–4998. https://doi.org/10.1074/jbc.M107345200
Giuliodori A, Beffagna G, Marchetto G, Fornetto C, Vanzi F, Toppo S et al (2018) Loss of cardiac Wnt/beta-catenin signalling in desmoplakin-deficient AC8 zebrafish models is rescuable by genetic and pharmacological intervention. Cardiovasc Res 114(8):1082–1097. https://doi.org/10.1093/cvr/cvy057
Gurney AM (2000) Electrophysiological recording methods used in vascular biology. J Pharmacol Toxicol Methods 44(2):409–420. https://doi.org/10.1016/s1056-8719(00)00120-9
Hassel D, Scholz EP, Trano N, Friedrich O, Just S, Meder B et al (2008) Deficient zebrafish ether-a-go-go-related gene channel gating causes short-QT syndrome in zebrafish reggae mutants. Circulation 117(7):866–875. https://doi.org/10.1161/CIRCULATIONAHA.107.752220
Haverinen J, Hassinen M, Dash SN, Vornanen M (2018) Expression of calcium channel transcripts in the zebrafish heart: dominance of T-type channels. J Exp Biol 221(Pt 10). https://doi.org/10.1242/jeb.179226
Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T et al (2006) Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 79(6):1081–1088. https://doi.org/10.1086/509044
Hoshijima K, Jurynec MJ, Klatt Shaw D, Jacobi AM, Behlke MA, Grunwald DJ (2019) Highly efficient CRISPR-Cas9-based methods for generating deletion mutations and F0 embryos that lack gene function in zebrafish. Dev Cell 51(5):645–657.e4. https://doi.org/10.1016/j.devcel.2019.10.004
Hosseini SM, Kim R, Udupa S, Costain G, Jobling R, Liston E et al (2018) Reappraisal of reported genes for sudden arrhythmic death: evidence-based evaluation of gene validity for Brugada syndrome. Circulation 138(12):1195–1205. https://doi.org/10.1161/CIRCULATIONAHA.118.035070
Hou JH, Kralj JM, Douglass AD, Engert F, Cohen AE (2014) Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents. Front Physiol 5:344. https://doi.org/10.3389/fphys.2014.00344
Huang CL (2017) Murine electrophysiological models of cardiac arrhythmogenesis. Physiol Rev 97(1):283–409. https://doi.org/10.1152/physrev.00007.2016
Huttner IG, Trivedi G, Jacoby A, Mann SA, Vandenberg JI, Fatkin D (2013) A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death. J Mol Cell Cardiol 61:123–132. https://doi.org/10.1016/j.yjmcc.2013.06.005
Ingles J, Macciocca I, Morales A, Thomson K (2020) Genetic testing in inherited heart diseases. Heart Lung Circ 29(4):505–511. https://doi.org/10.1016/j.hlc.2019.10.014
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096):816–821. https://doi.org/10.1126/science.1225829
Joris M, Schloesser M, Baurain D, Hanikenne M, Muller M, Motte P (2017) Number of inadvertent RNA targets for morpholino knockdown in Danio rerio is largely underestimated: evidence from the study of Ser/Arg-rich splicing factors. Nucleic Acids Res 45(16):9547–9557. https://doi.org/10.1093/nar/gkx638
Jou CJ, Spitzer KW, Tristani-Firouzi M (2010) Blebbistatin effectively uncouples the excitation-contraction process in zebrafish embryonic heart. Cell Physiol Biochem 25(4-5):419–424. https://doi.org/10.1159/000303046
Jou CJ, Barnett SM, Bian JT, Weng HC, Sheng X, Tristani-Firouzi M (2013) An in vivo cardiac assay to determine the functional consequences of putative long QT syndrome mutations. Circ Res 112(5):826–830. https://doi.org/10.1161/CIRCRESAHA.112.300664
Juang JJ, Binda A, Lee SJ, Hwang JJ, Chen WJ, Liu YB et al (2020) GSTM3 variant is a novel genetic modifier in Brugada syndrome, a disease with risk of sudden cardiac death. EBioMedicine 57:102843. https://doi.org/10.1016/j.ebiom.2020.102843
Kaese S, Verheule S (2012) Cardiac electrophysiology in mice: a matter of size. Front Physiol 3:345. https://doi.org/10.3389/fphys.2012.00345
Kamachi Y, Okuda Y, Kondoh H (2008) Quantitative assessment of the knockdown efficiency of morpholino antisense oligonucleotides in zebrafish embryos using a luciferase assay. Genesis 46(1):1–7. https://doi.org/10.1002/dvg.20361
Kapoor A, Sekar RB, Hansen NF, Fox-Talbot K, Morley M, Pihur V et al (2014) An enhancer polymorphism at the cardiomyocyte intercalated disc protein NOS1AP locus is a major regulator of the QT interval. Am J Hum Genet 94(6):854–869. https://doi.org/10.1016/j.ajhg.2014.05.001
Kawakami K (2007) Tol2: a versatile gene transfer vector in vertebrates. Genome Biol 8(Suppl 1):S7. https://doi.org/10.1186/gb-2007-8-s1-s7
Koopman CD, De Angelis J, Iyer SP, Verkerk AO, Da Silva J, Berecki G et al (2021) The zebrafish grime mutant uncovers an evolutionarily conserved role for Tmem161b in the control of cardiac rhythm. Proc Natl Acad Sci U S A 118(9). https://doi.org/10.1073/pnas.2018220118
Kopp R, Schwerte T, Pelster B (2005) Cardiac performance in the zebrafish breakdance mutant. J Exp Biol 208(Pt 11):2123–2134. https://doi.org/10.1242/jeb.01620
Langenbacher AD, Dong Y, Shu X, Choi J, Nicoll DA, Goldhaber JI et al (2005) Mutation in sodium-calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish. Proc Natl Acad Sci U S A 102(49):17699–17704. https://doi.org/10.1073/pnas.0502679102
Langenbacher AD, Shimizu H, Hsu W, Zhao Y, Borges A, Koehler C et al (2020) Mitochondrial calcium uniporter deficiency in zebrafish causes cardiomyopathy with arrhythmia. Front Physiol 11:617492. https://doi.org/10.3389/fphys.2020.617492
Langheinrich U, Vacun G, Wagner T (2003) Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia. Toxicol Appl Pharmacol 193(3):370–382. https://doi.org/10.1016/j.taap.2003.07.012
Leong IU, Skinner JR, Shelling AN, Love DR (2013) Expression of a mutant kcnj2 gene transcript in zebrafish. ISRN Mol Biol 2013:324839. https://doi.org/10.1155/2013/324839
Lin E, Ribeiro A, Ding W, Hove-Madsen L, Sarunic MV, Beg MF et al (2014) Optical mapping of the electrical activity of isolated adult zebrafish hearts: acute effects of temperature. Am J Physiol Regul Integr Comp Physiol 306(11):R823–R836. https://doi.org/10.1152/ajpregu.00002.2014
Lin E, Craig C, Lamothe M, Sarunic MV, Beg MF, Tibbits GF (2015) Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation. Am J Physiol Regul Integr Comp Physiol 308(9):R755–R768. https://doi.org/10.1152/ajpregu.00001.2015
Liu CC, Li L, Lam YW, Siu CW, Cheng SH (2016) Improvement of surface ECG recording in adult zebrafish reveals that the value of this model exceeds our expectation. Sci Rep 6:25073. https://doi.org/10.1038/srep25073
MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discov 14(10):721–731. https://doi.org/10.1038/nrd4627
Martin ED, Moriarty MA, Byrnes L, Grealy M (2009) Plakoglobin has both structural and signalling roles in zebrafish development. Dev Biol 327(1):83–96. https://doi.org/10.1016/j.ydbio.2008.11.036
Meder B, Scholz EP, Hassel D, Wolff C, Just S, Berger IM et al (2011) Reconstitution of defective protein trafficking rescues Long-QT syndrome in zebrafish. Biochem Biophys Res Commun 408(2):218–224. https://doi.org/10.1016/j.bbrc.2011.03.121
Milan DJ, Jones IL, Ellinor PT, MacRae CA (2006) In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation. Am J Physiol Heart Circ Physiol 291(1):H269–H273. https://doi.org/10.1152/ajpheart.00960.2005
Milosevic MM, Jang J, McKimm EJ, Zhu MH, Antic SD (2020) In vitro testing of voltage indicators: Archon1, ArcLightD, ASAP1, ASAP2s, ASAP3b, Bongwoori-Pos6, BeRST1, FlicR1, and Chi-VSFP-butterfly. eNeuro 7(5). https://doi.org/10.1523/ENEURO.0060-20.2020
Moriarty MA, Ryan R, Lalor P, Dockery P, Byrnes L, Grealy M (2012) Loss of plakophilin 2 disrupts heart development in zebrafish. Int J Dev Biol 56(9):711–718. https://doi.org/10.1387/ijdb.113390mm
Moro E, Vettori A, Porazzi P, Schiavone M, Rampazzo E, Casari A et al (2013) Generation and application of signaling pathway reporter lines in zebrafish. Mol Gen Genomics 288(5-6):231–242. https://doi.org/10.1007/s00438-013-0750-z
Mutoh H, Mishina Y, Gallero-Salas Y, Knopfel T (2015) Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging. Front Cell Neurosci 9:147. https://doi.org/10.3389/fncel.2015.00147
Nemtsas P, Wettwer E, Christ T, Weidinger G, Ravens U (2010) Adult zebrafish heart as a model for human heart? An electrophysiological study. J Mol Cell Cardiol 48(1):161–171. https://doi.org/10.1016/j.yjmcc.2009.08.034
Nerbonne JM, Nichols CG, Schwarz TL, Escande D (2001) Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here? Circ Res 89(11):944–956. https://doi.org/10.1161/hh2301.100349
Peal DS, Mills RW, Lynch SN, Mosley JM, Lim E, Ellinor PT et al (2011) Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen. Circulation 123(1):23–30. https://doi.org/10.1161/CIRCULATIONAHA.110.003731
Poon KL, Brand T (2013) The zebrafish model system in cardiovascular research: a tiny fish with mighty prospects. Glob Cardiol Sci Pract 2013(1):9–28. https://doi.org/10.5339/gcsp.2013.4
Pott A, Bock S, Berger IM, Frese K, Dahme T, Kessler M et al (2018) Mutation of the Na(+)/K(+)-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish. J Mol Cell Cardiol 120:42–52. https://doi.org/10.1016/j.yjmcc.2018.05.005
Prykhozhij SV, Fuller C, Steele SL, Veinotte CJ, Razaghi B, Robitaille JM et al (2018) Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9. Nucleic Acids Res 46(17):9252. https://doi.org/10.1093/nar/gky674
Rafferty SA, Quinn TA (2018) A beginner’s guide to understanding and implementing the genetic modification of zebrafish. Prog Biophys Mol Biol 138:3–19. https://doi.org/10.1016/j.pbiomolbio.2018.07.005
Ramachandran KV, Hennessey JA, Barnett AS, Yin X, Stadt HA, Foster E et al (2013) Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development. J Clin Invest 123(4):1638–1646. https://doi.org/10.1172/JCI66903
Ravens U (2018) Ionic basis of cardiac electrophysiology in zebrafish compared to human hearts. Prog Biophys Mol Biol 138:38–44. https://doi.org/10.1016/j.pbiomolbio.2018.06.008
Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S, Kruger M et al (2015) Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524(7564):230–233. https://doi.org/10.1038/nature14580
Rottbauer W, Baker K, Wo ZG, Mohideen MA, Cantiello HF, Fishman MC (2001) Growth and function of the embryonic heart depend upon the cardiac-specific L-type calcium channel alpha1 subunit. Dev Cell 1(2):265–275. https://doi.org/10.1016/s1534-5807(01)00023-5
Sakmann B, Neher E (1984) Patch clamp techniques for studying ionic channels in excitable membranes. Annu Rev Physiol 46:455–472. https://doi.org/10.1146/annurev.ph.46.030184.002323
Shaheen N, Shiti A, Gepstein L (2017) Pluripotent stem cell-based platforms in cardiac disease modeling and drug testing. Clin Pharmacol Ther 102(2):203–208. https://doi.org/10.1002/cpt.722
Shen Y, Nasu Y, Shkolnikov I, Kim A, Campbell RE (2020) Engineering genetically encoded fluorescent indicators for imaging of neuronal activity: progress and prospects. Neurosci Res 152:3–14. https://doi.org/10.1016/j.neures.2020.01.011
Shimizu H, Schredelseker J, Huang J, Lu K, Naghdi S, Lu F et al (2015) Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity. eLife 4. https://doi.org/10.7554/eLife.04801
Shu X, Cheng K, Patel N, Chen F, Joseph E, Tsai HJ et al (2003) Na,K-ATPase is essential for embryonic heart development in the zebrafish. Development 130(25):6165–6173. https://doi.org/10.1242/dev.00844
Skarsfeldt MA, Bomholtz SH, Lundegaard PR, Lopez-Izquierdo A, Tristani-Firouzi M, Bentzen BH (2018) Atrium-specific ion channels in the zebrafish-a role of IKACh in atrial repolarization. Acta Physiol (Oxf) 223(3):e13049. https://doi.org/10.1111/apha.13049
Smeland MF, McClenaghan C, Roessler HI, Savelberg S, Hansen GAM, Hjellnes H et al (2019) ABCC9-related intellectual disability myopathy syndrome is a KATP channelopathy with loss-of-function mutations in ABCC9. Nat Commun 10(1):4457. https://doi.org/10.1038/s41467-019-12428-7
Sondergaard MT, Sorensen AB, Skov LL, Kjaer-Sorensen K, Bauer MC, Nyegaard M et al (2015) Calmodulin mutations causing catecholaminergic polymorphic ventricular tachycardia confer opposing functional and biophysical molecular changes. FEBS J 282(4):803–816. https://doi.org/10.1111/febs.13184
Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS et al (2017) Guidelines for morpholino use in zebrafish. PLoS Genet 13(10):e1007000. https://doi.org/10.1371/journal.pgen.1007000
Tanaka Y, Hayashi K, Fujino N, Konno T, Tada H, Nakanishi C et al (2019) Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography. Heart Vessel 34(1):159–166. https://doi.org/10.1007/s00380-018-1231-4
Tessadori F, van Weerd JH, Burkhard SB, Verkerk AO, de Pater E, Boukens BJ et al (2012) Identification and functional characterization of cardiac pacemaker cells in zebrafish. PLoS One 7(10):e47644. https://doi.org/10.1371/journal.pone.0047644
Tessadori F, Roessler HI, Savelberg SMC, Chocron S, Kamel SM, Duran KJ et al (2018) Effective CRISPR/Cas9-based nucleotide editing in zebrafish to model human genetic cardiovascular disorders. Dis Model Mech 11(10). https://doi.org/10.1242/dmm.035469
Tessadori F, de Bakker DEM, Barske L, Nelson N, Algra HA, Willekers S et al (2020) Zebrafish prrx1a mutants have normal hearts. Nature 585(7826):E14–EE6. https://doi.org/10.1038/s41586-020-2674-1
Thorsen K, Dam VS, Kjaer-Sorensen K, Pedersen LN, Skeberdis VA, Jurevicius J et al (2017) Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nat Commun 8(1):1696. https://doi.org/10.1038/s41467-017-01630-0
Tsai CT, Wu CK, Chiang FT, Tseng CD, Lee JK, Yu CC et al (2011) In-vitro recording of adult zebrafish heart electrocardiogram - a platform for pharmacological testing. Clin Chim Acta 412(21–22):1963–1967. https://doi.org/10.1016/j.cca.2011.07.002
Tsutsui H, Higashijima S, Miyawaki A, Okamura Y (2010) Visualizing voltage dynamics in zebrafish heart. J Physiol 588(Pt 12):2017–2021. https://doi.org/10.1113/jphysiol.2010.189126
van den Boogaard M, Wong LY, Tessadori F, Bakker ML, Dreizehnter LK, Wakker V et al (2012) Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer. J Clin Invest 122(7):2519–2530. https://doi.org/10.1172/JCI62613
van Opbergen CJM, Koopman CD, Kok BJM, Knopfel T, Renninger SL, Orger MB et al (2018) Optogenetic sensors in the zebrafish heart: a novel in vivo electrophysiological tool to study cardiac arrhythmogenesis. Theranostics 8(17):4750–4764. https://doi.org/10.7150/thno.26108
Varshney GK, Pei W, LaFave MC, Idol J, Xu L, Gallardo V et al (2015) High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Res 25(7):1030–1042. https://doi.org/10.1101/gr.186379.114
Verkerk AO, Remme CA (2012) Zebrafish: a novel research tool for cardiac (patho)electrophysiology and ion channel disorders. Front Physiol 3:255. https://doi.org/10.3389/fphys.2012.00255
Vornanen M, Hassinen M (2016) Zebrafish heart as a model for human cardiac electrophysiology. Channels (Austin) 10(2):101–110. https://doi.org/10.1080/19336950.2015.1121335
Wang YT, Gu S, Rollins AM, Jenkins MW (2013) Optical mapping of optically paced embryonic hearts. Annu Int Conf IEEE Eng Med Biol Soc 2013:1623–1626. https://doi.org/10.1109/EMBC.2013.6609827
Warren KS, Baker K, Fishman MC (2001) The slow mo mutation reduces pacemaker current and heart rate in adult zebrafish. Am J Physiol Heart Circ Physiol 281(4):H1711–H1719. https://doi.org/10.1152/ajpheart.2001.281.4.H1711
Weber M, Scherf N, Meyer AM, Panakova D, Kohl P, Huisken J (2017) Cell-accurate optical mapping across the entire developing heart. eLife 6. https://doi.org/10.7554/eLife.28307
Wickenden AD (2014) Overview of electrophysiological techniques. Curr Protoc Pharmacol 64:11.1.1–11.1.17. https://doi.org/10.1002/0471141755.ph1101s64
Wu RS, Lam II, Clay H, Duong DN, Deo RC, Coughlin SR (2018) A rapid method for directed gene knockout for screening in G0 zebrafish. Dev Cell 46(1):112–125.e4. https://doi.org/10.1016/j.devcel.2018.06.003
Yuan S, Joseph EM (2004) The small heart mutation reveals novel roles of Na+/K+-ATPase in maintaining ventricular cardiomyocyte morphology and viability in zebrafish. Circ Res 95(6):595–603. https://doi.org/10.1161/01.RES.0000141529.48143.6e
Zhang PC, Llach A, Sheng XY, Hove-Madsen L, Tibbits GF (2011) Calcium handling in zebrafish ventricular myocytes. Am J Physiol Regul Integr Comp Physiol 300(1):R56–R66. https://doi.org/10.1152/ajpregu.00377.2010
Zhou P, Yang X, Li C, Gao Y, Hu D (2010) Quinidine depresses the transmural electrical heterogeneity of transient outward potassium current of the right ventricular outflow tract free wall. J Cardiovasc Dis Res 1(1):12–18. https://doi.org/10.4103/0975-3583.59979
Zhou J, Wang L, Zuo M, Wang X, Ahmed AS, Chen Q et al (2016) Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm. Sci Rep 6:21538. https://doi.org/10.1038/srep21538
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Sieliwonczyk, E. et al. (2021). Inherited Ventricular Arrhythmia in Zebrafish: Genetic Models and Phenotyping Tools. In: Pedersen, S.H.F. (eds) Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 184. Springer, Cham. https://doi.org/10.1007/112_2021_65
Download citation
DOI: https://doi.org/10.1007/112_2021_65
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-24203-8
Online ISBN: 978-3-031-24204-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)