Abstract
Cardiomyopathy refers to the cardiac remodeling process in response to a variety of intrinsic and extrinsic stimuli that stress the heart. To discover novel therapeutic strategies for the disease, we are establishing and characterizing adult zebrafish models of cardiomyopathy. One of the models is tr265/tr265, a line that becomes anemic due to a mutation that ablates erythroid-specific Band 3 protein. Although Band 3 does not express in the heart, the chronic anemic stress induces profound cardiac enlargement and cardiomyopathy-like pathogenesis. Phenylhydrazine hydrochloride (PHZ)-induced anemia model has been established which enables application of anemia stress to any adult fish. In this chapter, we provide detailed information on generation of two anemic models in zebrafish; measurement of the anemia level; determination of enlarged hearts in either organ level or cellular level; and detection of cardiomyocyte hyperplasia, as well as survival rate recording. The protocols described here can be applied to other adult zebrafish models of cardiomyopathy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ahmad F, Seidman JG, Seidman CE (2005) The genetic basis for cardiac remodeling. Annu Rev Genomics Hum Genet 6:185–216
Hasenfuss G (1998) Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc Res 39:60–76
Molkentin JD, Robbins J (2008) With great power comes great responsibility: using mouse genetics to study cardiac hypertrophy and failure. J Mol Cell Cardiol 46:130–136
Wolf MJ, Amrein H, Izatt JA, Choma MA, Reedy MC, Rockman HA (2006) Drosophila as a model for the identification of genes causing adult human heart disease. Proc Natl Acad Sci USA 103:1394–1399
Chen JN, Haffter P, Odenthal J, Vogelsang E, Brand M, van Eeden FJ, Furutani-Seiki M, Granato M, Hammerschmidt M, Heisenberg CP, Jiang YJ, Kane DA, Kelsh RN, Mullins MC, Nusslein-Volhard C (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development 123:293–302
Stainier DY, Fouquet B, Chen JN, Warren KS, Weinstein BM, Meiler SE, Mohideen MA, Neuhauss SC, Solnica-Krezel L, Schier AF, Zwartkruis F, Stemple DL, Malicki J, Driever W, Fishman MC (1996) Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. Development 123:285–292
Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44
Stainier DY (2001) Zebrafish genetics and vertebrate heart formation. Nat Rev Genet 2:39–48
Chico TJ, Ingham PW, Crossman DC (2008) Modeling cardiovascular disease in the zebrafish. Trends Cardiovasc Med 4:150–155
Sun X, Hoage T, Bai P, Ding Y, Chen Z, Zhang R, Huang W, Jahangir A, Paw B, Li YG, Xu X (2009) Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish. PLoS One 4:e6596
Paw BH, Davidson AJ, Zhou Y, Li R, Pratt SJ, Lee C, Trede NS, Brownlie A, Donovan A, Liao EC, Ziai JM, Drejer AH, Guo W, Kim CH, Gwynn B, Peters LL, Chernova MN, Alper SL, Zapata A, Wickramasinghe SN, Lee MJ, Lux SE, Fritz A, Postlethwait JH, Zon LI (2003) Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency. Nat Genet 34:59–64
Ding Y, Sun X, Huang W, Hoage T, Redfield M, Kushwaha S, Sivasubbu S, Lin X, Ekker S, Xu X (2011) Haploinsufficiency of target of rapamycin attenuates cardiomyopathies in adult zebrafish. Circ Res 109:658–669
Simunek T, Sterba M, Popelova O, Adamcova M, Hrdina R, Gersl V (2009) Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 61:154–171
Christiansen S, Autschbach R (2006) Doxorubicin in experimental and clinical heart failure. Eur J Cardiothorac Surg 30:611–616
Yi X, Bekeredjian R, DeFilippis NJ, Siddiquee Z, Fernandez E, Shohet RV (2006) Transcriptional analysis of doxorubicin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol 290:H1098–H1102
Robert J (2007) Preclinical assessment of anthracycline cardiotoxicity in laboratory animals: predictiveness and pitfalls. Cell Biol Toxicol 23:27–37
Norman TD, Mc BR (1958) Cardiac hypertrophy in rats with phenylhydrazine anemia. Circ Res 6:765–770
Simonot DL, Farrell AP (2007) Cardiac remodelling in rainbow trout Oncorhynchus mykiss Walbaum in response to phenylhydrazine-induced anaemia. J Exp Biol 210:2574–2584
Danilova N, Sakamoto KM, Lin S (2008) Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood 112:5228–5237
Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Develop Dynam 203:253–350
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Sun, X., Xu, X. (2012). Anemic Zebrafish Models of Cardiomyopathy. In: Szallasi, A., BÃró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-095-3_2
Download citation
DOI: https://doi.org/10.1007/978-1-62703-095-3_2
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-094-6
Online ISBN: 978-1-62703-095-3
eBook Packages: Springer Protocols