Animal models of arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathies are a heterogeneous group of pathological conditions that give rise to myocardial dysfunction with an increased risk for atrial or ventricular arrhythmias. Inherited defects in cardiomyocyte proteins in the sarcomeric contractile apparatus, the cytoskeleton and desmosomal cell-cell contact junctions are becoming recognized increasingly as major causes of sudden cardiac death in the general population. Animal models have been developed for the systematic dissection of the genetic pathways involved in the pathogenesis of arrhythmogenic cardiomyopathies. This review presents an overview of current animal models for arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) associated with cardiac arrhythmias and sudden cardiac death.

[1]  Y. Oade,et al.  Arrhythmogenic right ventricular cardiomyopathy , 2011, BMJ Case Reports.

[2]  R. Pazoki,et al.  Genetic Basis of Ventricular Arrhythmias , 2010, Current cardiovascular risk reports.

[3]  L. Byrnes,et al.  Plakoglobin has both structural and signalling roles in zebrafish development. , 2009, Developmental biology.

[4]  Ju Chen,et al.  Cardiac-specific ablation of Cypher leads to a severe form of dilated cardiomyopathy with premature death. , 2009, Human molecular genetics.

[5]  Veniamin Y Sidorov,et al.  Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. , 2008, The Journal of clinical investigation.

[6]  W. Giles,et al.  Cardiac troponin T mutations promote life-threatening arrhythmias. , 2008, The Journal of clinical investigation.

[7]  A. Moorman,et al.  Developmental Basis for Electrophysiological Heterogeneity in the Ventricular and Outflow Tract Myocardium As a Substrate for Life-Threatening Ventricular Arrhythmias , 2008, Circulation research.

[8]  K. Nishii,et al.  Targeted disruption of the cardiac troponin T gene causes sarcomere disassembly and defects in heartbeat within the early mouse embryo. , 2008, Developmental biology.

[9]  C. Berul,et al.  Molecular Mechanisms of Inherited Arrhythmias , 2008, Current genomics.

[10]  A. Marian.  Genetic determinants of cardiac hypertrophy , 2008, Current opinion in cardiology.

[11]  H. Calkins,et al.  Mechanisms of Disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy , 2008, Nature Clinical Practice Cardiovascular Medicine.

[12]  J. Seidman,et al.  Severe Heart Failure and Early Mortality in a Double-Mutation Mouse Model of Familial Hypertrophic Cardiomyopathy , 2008, Circulation.

[13]  A. Keren,et al.  Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression , 2008, Nature Clinical Practice Cardiovascular Medicine.

[14]  M. Yano,et al.  Altered expression of connexin43 contributes to the arrhythmogenic substrate during the development of heart failure in cardiomyopathic hamster. , 2008, American journal of physiology. Heart and circulatory physiology.

[15]  Ferhaan Ahmad,et al.  Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease. , 2008, Journal of molecular and cellular cardiology.

[16]  I. Efimov,et al.  Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy , 2007, Circulation research.

[17]  D. Stokes.  Desmosomes from a structural perspective. , 2007, Current opinion in cell biology.

[18]  S. Rohr.  Molecular crosstalk between mechanical and electrical junctions at the intercalated disc. , 2007, Circulation research.

[19]  Joel C. Miller,et al.  Cardiac-Myocyte-Specific Excision of the Vinculin Gene Disrupts Cellular Junctions, Causing Sudden Death or Dilated Cardiomyopathy , 2007, Molecular and Cellular Biology.

[20]  C. Patterson.  Faculty Opinions recommendation of Gi alpha 1-mediated cardiac electrophysiological remodeling and arrhythmia in hypertrophic cardiomyopathy. , 2007 .

[21]  Lai-Hua Xie,et al.  Giα1-Mediated Cardiac Electrophysiological Remodeling and Arrhythmia in Hypertrophic Cardiomyopathy , 2007, Circulation.

[22]  X. Wehrens.  The molecular basis of catecholaminergic polymorphic ventricular tachycardia: what are the different hypotheses regarding mechanisms? , 2007, Heart rhythm.

[23]  E. Moric-Janiszewska,et al.  Review on the genetics of arrhythmogenic right ventricular dysplasia. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[24]  P. Ellinor,et al.  Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. , 2006, American journal of human genetics.

[25]  J. Towbin,et al.  The mystery of arrhythmogenic right ventricular dysplasia/cardiomyopathy: from observation to mechanistic explanation. , 2006, Circulation.

[26]  G. Breithardt,et al.  Age- and Training-Dependent Development of Arrhythmogenic Right Ventricular Cardiomyopathy in Heterozygous Plakoglobin-Deficient Mice , 2006, Circulation.

[27]  D. Allen,et al.  Molecular insights from a novel cardiac troponin I mouse model of familial hypertrophic cardiomyopathy. , 2006, Journal of molecular and cellular cardiology.

[28]  Ferhaan Ahmad,et al.  Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function , 2006, Proceedings of the National Academy of Sciences.

[29]  Hugh Calkins,et al.  Desmosomal Dysfunction due to Mutations in Desmoplakin Causes Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy , 2006, Circulation research.

[30]  Wei Zhang,et al.  Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy , 2006, Proceedings of the National Academy of Sciences.

[31]  Michael D. Schneider,et al.  Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. , 2006, The Journal of clinical investigation.

[32]  W. Birchmeier,et al.  Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism. , 2006, The Journal of clinical investigation.

[33]  P. Reiser,et al.  Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts , 2006, Human Genetics.

[34]  Eric L. Anderson.  Arrhythmogenic Right Ventricular Dyplasia , 2006 .

[35]  Barry J Maron,et al.  Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interd , 2006, Circulation.

[36]  G. Dorn,et al.  A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Christopher Semsarian,et al.  Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  P. Nallari,et al.  Etiopathogenesis of arrhythmogenic right ventricular cardiomyopathy , 2005, Journal of Human Genetics.

[39]  J. Rottman,et al.  Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice. , 2005, Human molecular genetics.

[40]  W. Birchmeier,et al.  Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation , 2004, The Journal of cell biology.

[41]  S. Ekker,et al.  Zebrafish as a genomics research model. , 2004, Current pharmaceutical biotechnology.

[42]  Y. Sherer,et al.  Arrhythmogenic right ventricular dysplasia: a possible cause of sudden incapacitation. , 2004, Aviation, space, and environmental medicine.

[43]  Jeffrey A. Towbin,et al.  Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs: A New Animal Model of Human Disease , 2004, Circulation.

[44]  Y. Kaneda,et al.  Lamr1 functional retroposon causes right ventricular dysplasia in mice , 2004, Nature Genetics.

[45]  M. Lohse,et al.  Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy. , 2003, American journal of physiology. Heart and circulatory physiology.

[46]  K. Nakao,et al.  NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function , 2003, The EMBO journal.

[47]  C. Berul.  Electrophysiological phenotyping in genetically engineered mice. , 2003, Physiological genomics.

[48]  P. Kirchhof,et al.  Familial Hypertrophic Cardiomyopathy-Linked Mutant Troponin T Causes Stress-Induced Ventricular Tachycardia and Ca2+-Dependent Action Potential Remodeling , 2003, Circulation research.

[49]  J. Seidman,et al.  Ventricular Arrhythmia Vulnerability in Cardiomyopathic Mice With Homozygous Mutant Myosin-Binding Protein C Gene , 2001, Circulation.

[50]  Qiang Zhou,et al.  Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy , 2001, The Journal of cell biology.

[51]  D. Szczesna,et al.  Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy. , 2001, The Journal of biological chemistry.

[52]  D. Stephan,et al.  Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). , 2001, Human molecular genetics.

[53]  H. Katus,et al.  Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias. , 2000, Cardiovascular research.

[54]  Neil E. Bowles,et al.  The “Final Common Pathway” Hypothesis and Inherited Cardiovascular Disease The Role of Cytoskeletal Proteins in Dilated Cardiomyopathy , 2000, Herz.

[55]  A J Marian,et al.  A transgenic rabbit model for human hypertrophic cardiomyopathy. , 1999, The Journal of clinical investigation.

[56]  J. Towbin,et al.  Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease. , 1999, Circulation.

[57]  A. Lochner,et al.  Work Performance of the Isolated Perfused Beating Heart in the Hereditary Myocardiopathy of the Syrian Hamster , 1967, Circulation research.

[58]  V. Barrios,et al.  Arrhythmogenic right ventricular dysplasia. , 2009, Journal of the American College of Cardiology.

[59]  S. Morimoto.  Sarcomeric proteins and inherited cardiomyopathies. , 2008, Cardiovascular research.

[60]  M. Hatzfeld.  Plakophilins: Multifunctional proteins or just regulators of desmosomal adhesion? , 2007, Biochimica et biophysica acta.