A new mouse cardiac electrophysiology method was used to study mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. Wild-type animals had completely normal cardiac electrophysiology. In contrast, FHC mice demonstrated (a) electrocardiographic abnormalities including prolonged repolarization intervals and rightward axis; (b) electrophysiological abnormalities including heterogeneous ventricular conduction properties and prolonged sinus node recovery time; and (c) inducible ventricular ectopy. These data identify distinct electrophysiologic abnormalities in FHC mice with a specific alpha-myosin mutation, and also validate a novel method to explore in vivo the relationship between specific genotypes and their electrophysiologic phenotypes.
C I Berul, M E Christe, M J Aronovitz, C E Seidman, J G Seidman, M E Mendelsohn
Title and authors | Publication | Year |
---|---|---|
Autoimmune Atrial Fibrillation.
Maguy A, Mahendran Y, Tardif JC, Busseuil D, Li J |
Circulation | 2023 |
Unraveling the Genotype‐Phenotype Relationship in Hypertrophic Cardiomyopathy: Obesity‐Related Cardiac Defects as a Major Disease Modifier
EE Nollet, BD Westenbrink, RA de Boer, DW Kuster, J van der Velden |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2020 |
Sex related differences in the pathogenesis of organ fibrosis
A Garate-Carrillo, J Gonzalez, G Ceballos, I Ramirez-Sanchez, F Villarreal |
Translational research : the journal of laboratory and clinical medicine | 2020 |
Early remodeling of repolarizing K + currents in the αMHC 403/+ mouse model of familial hypertrophic cardiomyopathy
R Hueneke, A Adenwala, RL Mellor, JG Seidman, CE Seidman, JM Nerbonne |
Journal of Molecular and Cellular Cardiology | 2017 |
Murine Electrophysiological Models of Cardiac Arrhythmogenesis
CL Huang |
Physiological reviews | 2016 |
Slowed atrial and atrioventricular conduction and depressed HRV in a murine model of hypertrophic cardiomyopathy
WW Lim, M Baumert, M Neo, P Kuklik, AN Ganesan, DH Lau, T Tsoutsman, C Semsarian, P Sanders, DA Saint |
Clinical and Experimental Pharmacology and Physiology | 2015 |
Comprehensive Physiology
SN Cheuvront, RW Kenefick |
Comprehensive Physiology | 2014 |
Cardiac electrophysiology and the susceptibility to sustained ventricular tachycardia in intact, conscious mice
HL Lujan, SE DiCarlo |
American journal of physiology. Heart and circulatory physiology | 2014 |
Emery and Rimoin's Principles and Practice of Medical Genetics
DC Wallace, MT Lott, V Procaccio |
Emery and Rimoin's Principles and Practice of Medical Genetics | 2013 |
Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study
J Gomes, M Finlay, AK Ahmed, EJ Ciaccio, A Asimaki, JE Saffitz, G Quarta, M Nobles, P Syrris, S Chaubey, WJ McKenna, A Tinker, PD Lambiase |
European Heart Journal | 2012 |
The Laboratory Mouse
A Braun, H Ernst, D Schaudien, HG Hoymann, S Rittinghausen |
The Laboratory Mouse | 2012 |
Physical exercise reduces cardiac defects in type 2 spinal muscular atrophy-like mice: Physical exercise reduces cardiac defects in spinal muscular atrophy
O Biondi, P Lopes, C Desseille, J Branchu, F Chali, AB Salah, C Pariset, C Chanoine, F Charbonnier |
The Journal of Physiology | 2012 |
Current Topics in Developmental Biology
JE Qualls, PJ Murray |
Cancer and Development | 2011 |
Improvements in the Establishment of a Rat Myocardial Infarction Model
Y Hou, C Huang, X Cai, J Zhao, W Guo |
J INT MED RES | 2011 |
Influence of sex hormones and phytoestrogens on heart disease in men and women
P Bhupathy, CD Haines, LA Leinwand |
Women's Health | 2010 |
Sex-Based Cardiac Physiology
ED Luczak, LA Leinwand |
Annual Review of Physiology | 2009 |
The tight junction protein CAR regulates cardiac conduction and cell-cell communication
U Lisewski, Y Shi, U Wrackmeyer, R Fischer, C Chen, A Schirdewan, R Jüttner, F Rathjen, W Poller, MH Radke, M Gotthardt |
Journal of Experimental Medicine | 2008 |
Reversibility of PRKAG2 Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations
CM Wolf, M Arad, F Ahmad, A Sanbe, SA Bernstein, O Toka, T Konno, G Morley, J Robbins, JG Seidman, CE Seidman, CI Berul |
Circulation | 2008 |
IMPACT OF MULTIPLE GENE MUTATIONS IN DETERMINING THE SEVERITY OF CARDIOMYOPATHY AND HEART FAILURE
T Tsoutsman, RD Bagnall, C Semsarian |
Clinical and Experimental Pharmacology and Physiology | 2008 |
Non-invasive restrained ECG recording in conscious small rodents: a new tool for cardiac electrical activity investigation
H Mongue-Din, A Salmon, MY Fiszman, Y Fromes |
Pflügers Archiv - European Journal of Physiology | 2007 |
Post-Genomic Cardiology
J Marín-García, MJ Goldenthal, GW Moe |
Post-Genomic Cardiology | 2007 |
Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy
W Chen, Y Wang, Y Abe, L Cheney, B Udd, YP Li |
Journal of Molecular Biology | 2007 |
GENES, CALCIUM AND MODIFYING FACTORS IN HYPERTROPHIC CARDIOMYOPATHY
T Tsoutsman, L Lam, C Semsarian |
Clinical and Experimental Pharmacology and Physiology | 2006 |
Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia
CM Wolf, IP Moskowitz, S Arno, DM Branco, C Semsarian, SA Bernstein, M Peterson, M Maida, GE Morley, G Fishman, CI Berul, CE Seidman, JG Seidman |
Proceedings of the National Academy of Sciences | 2005 |
Principles of Molecular Cardiology
MS Runge, C Patterson |
2005 | |
Thyroid hormone stimulates myoglobin gene expression in rat cardiac muscle
G Giannocco, RA DosSantos, MT Nunes |
Molecular and Cellular Endocrinology | 2004 |
Cardiac Electrophysiology
B London |
Cardiac Electrophysiology | 2004 |
Hypertrophic Cardiomyopathy: From “Heart Tumour” to a Complex Molecular Genetic Disorder
A Doolan, L Nguyen, C Semsarian |
Heart, Lung and Circulation | 2004 |
Cardiología pediátrica en la era de la genómica
J Marín-García |
Revista Española de Cardiología | 2004 |
Pediatric Cardiology in the Genomic Era
J Marín-García |
Revista Española de Cardiología (English Edition) | 2004 |
Genotype, phenotype: upstairs, downstairs in the family of cardiomyocytes
Kenneth Chien |
Journal of Clinical Investigation | 2003 |
Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5 transgenic mice
H Wakimoto, H Kasahara, CT Maguire, IP Moskowitz, S Izumo, CI Berul |
genesis | 2003 |
Hypertrophic cardiomyopathy: from gene defect to clinical disease
MW CHUNG, T TSOUTSMAN, C SEMSARIAN |
Cell Research | 2003 |
Cardiac Electrophysiologic Abnormalities in the CREBA133 Transgenic Mouse Model of Idiopathic Dilated Cardiomyopathy
W Zhu, JJ Lepore, S Saba, S Joseph, MS Link, MK Homoud, NM Estes, PJ Wang, JM Leiden |
Journal of Cardiovascular Electrophysiology | 2003 |
Analysis of the Corrected QT Before the Onset of Nonsustained Ventricular Tachycardia in Patients with Hypertrophic Cardiomyopathy
R Baranowski, L Chojnowska, E Michalak, E Orlowska-Baranowska |
Pacing and Clinical Electrophysiology | 2003 |
Cardiovascular and renal phenotyping of genetically modified mice: A challenge for traditional physiology
SM Fitzgerald, L Gan, A Wickman, G Bergstrom |
Clinical and Experimental Pharmacology and Physiology | 2003 |
Subdiaphragmatic murine electrophysiological studies: sequential determination of ventricular refractoriness and arrhythmia induction
DE Gutstein, SB Danik, JB Sereysky, GE Morley, GI Fishman |
American journal of physiology. Heart and circulatory physiology | 2003 |
Electrophysiological phenotyping in genetically engineered mice
CI Berul |
Physiological genomics | 2003 |
Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies
CT Maguire, H Wakimoto, VV Patel, PE Hammer, K Gauvreau, CI Berul |
Physiological genomics | 2003 |
A Mouse Model of Congenital Heart Disease: Cardiac Arrhythmias and Atrial Septal Defect Caused by Haploinsufficiency of the Cardiac Transcription Factor Csx/Nkx2.5
M Tanaka, C Berul, M Ishii, P Jay, H Wakimoto, P Douglas, N Yamasaki, T Kawamoto, J Gehrmann, C Maguire, M Schinke, C Seidman, J Seidman, Y Kurachi, S Izumo |
Cold Spring Harbor Symposia on Quantitative Biology | 2002 |
The MLP Family of Cytoskeletal Z Disc Proteins and Dilated Cardiomyopathy: A Stress Pathway Model for Heart Failure Progression
M Hoshijima, M Pashmforoush, R Knoll, K Chien |
Cold Spring Harbor Symposia on Quantitative Biology | 2002 |
Noninvasive Cardiovascular Phenotyping in Mice
CJ Hartley, GE Taffet, AK Reddy, ML Entman, LH Michael |
ILAR journal / National Research Council, Institute of Laboratory Animal Resources | 2002 |
Effects of all - trans retinoic acid on angiotensin II-induced myocyte hypertrophy
HJ Wang, YC Zhu, T Yao |
Journal of applied physiology | 2002 |
Correlation of repolarization of ventricular monophasic action potential with ECG in the murine heart
S Danik, C Cabo, C Chiello, S Kang, AL Wit, J Coromilas |
American journal of physiology. Heart and circulatory physiology | 2002 |
In-vivo electrophysiological study in mice with chronic anterior myocardial infarction
Thomas Korte, Martin Fuchs, Zeynep Guener, Joachim v Bonin, Marcos de Sousa, Michael Niehaus, Jürgen Tebbenjohanns, Helmut Drexler |
Journal of Interventional Cardiac Electrophysiology | 2002 |
The molecular genetic basis for hypertrophic cardiomyopathy
AJ Marian, R Roberts |
Journal of Molecular and Cellular Cardiology | 2001 |
Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression
BG Bruneau, ZZ Bao, D Fatkin, J Xavier-Neto, D Georgakopoulos, CT Maguire, CI Berul, DA Kass, ML Bold, AJ de Bold, DA Conner, N Rosenthal, CL Cepko, CE Seidman, JG Seidman |
Molecular and cellular biology | 2001 |
Molecular genetics and pathogenesis of hypertrophic cardiomyopathy
AJ Marian, L Salek, S Lutucuta |
Minerva medica | 2001 |
A Defect in the Kv Channel-Interacting Protein 2 (KChIP2) Gene Leads to a Complete Loss of Ito and Confers Susceptibility to Ventricular Tachycardia
HC Kuo, CF Cheng, RB Clark, JJ Lin, JL Lin, M Hoshijima, VT Nguyêñ-Trân, Y Gu, Y Ikeda, PH Chu, J Ross, WR Giles, KR Chien |
Cell | 2001 |
Heart Physiology and Pathophysiology
NS Dhalla, RM Temsah, T Netticadan, MS Sandhu |
Heart Physiology and Pathophysiology | 2001 |
Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with conscious echocardiographic approach
S Takuma, K Suehiro, C Cardinale, T Hozumi, H Yano, J Shimizu, S Mullis-Jansson, R Sciacca, J Wang, D Burkhoff, MR di Tullio, S Homma |
American journal of physiology. Heart and circulatory physiology | 2001 |
Characterization of mice with a combined suppression of Ito and IK,slow
M Brunner, W Guo, GF Mitchell, PD Buckett, JM Nerbonne, G Koren |
American journal of physiology. Heart and circulatory physiology | 2001 |
Ventricular Arrhythmia Vulnerability in Cardiomyopathic Mice With Homozygous Mutant Myosin-Binding Protein C Gene
CI Berul, BK McConnell, H Wakimoto, IP Moskowitz, CT Maguire, C Semsarian, MM Vargas, J Gehrmann, CE Seidman, JG Seidman |
Circulation | 2001 |
Cardiovascular Physiology in the Genetically Engineered Mouse
BD Hoit, RA Walsh |
2001 | |
Potassium Channels in Cardiovascular Biology
SL Archer, NJ Rusch |
2001 | |
Cardiac Electrophysiology in Genetically Engineered Mice
J Gehrmann, CI Berul |
Journal of Cardiovascular Electrophysiology | 2000 |
Animal models of hypertrophic cardiomyopathy
A Maass, LA Leinwand |
Current Opinion in Cardiology | 2000 |
Remodeling the Cardiac Sarcomere Using Transgenesis
J Robbins |
Annual Review of Physiology | 2000 |
Remodelling of ionic currents in hypertrophied and failing hearts of transgenic mice overexpressing calsequestrin
BC Knollmann, BE Knollmann-Ritschel, NJ Weissman, LR Jones, M Morad |
The Journal of Physiology | 2000 |
Commentary on the Special Topic Section on the Use of Transgenic Models
EG Kranias |
Annual Review of Physiology | 2000 |
Identificación y tratamiento de los pacientes con miocardiopatía hipertrófica y riesgo de muerte súbita
WJ McKenna, LM Iglesias |
Revista Española de Cardiología | 2000 |
Analysis of organ physiology in transgenic mice
S Rao, AS Verkman |
American journal of physiology. Cell physiology | 2000 |
Molecular Genetics of Cardiac Electrophysiology
CI Berul, JA Towbin |
2000 | |
DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model
CI Berul, CT Maguire, MJ Aronovitz, J Greenwood, C Miller, J Gehrmann, D Housman, ME Mendelsohn, S Reddy |
Journal of Clinical Investigation | 1999 |
A Gap in Understanding the Connection Between Connexins and Cardiac Conduction
CI Berul |
Journal of Cardiovascular Electrophysiology | 1999 |
Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype?
EN Olson, JD Molkentin |
Circulation research | 1999 |
QT Dispersion in α-Myosin Heavy-Chain Familial Hypertrophic Cardiomyopathy Mice
LM Bevilacqua, CT Maguire, JG Seidman, CE Seidman, CI Berul |
Pediatric Research | 1999 |
Assessment of atrioventricular nodal physiology in the mouse
B A VanderBrink, M S Link, M J Aronovitz, S Saba, S B Sloan, M K Homoud, N A Estes III, P J Wang |
Journal of Interventional Cardiac Electrophysiology | 1999 |
Diastolic dysfunction and altered energetics in the alphaMHC403/+ mouse model of familial hypertrophic cardiomyopathy
M Spindler, KW Saupe, ME Christe, HL Sweeney, CE Seidman, JG Seidman, JS Ingwall |
Journal of Clinical Investigation | 1998 |
Molecular Genetic Basis of Hypertrophic Cardiomyopathy:
AJ Marian, R Roberts |
Journal of Cardiovascular Electrophysiology | 1998 |
Conditional lineage ablation to model human diseases
P Lee, G Morley, Q Huang, A Fischer, S Seiler, JW Horner, S Factor, D Vaidya, J Jalife, GI Fishman |
Proceedings of the National Academy of Sciences | 1998 |
Familial Sick Sinus Syndrome With Atrioventricular Conduction Disturbance
M Isobe, T Oka, H Takenaka, H Imamura, O Kinoshita, H Kasanuki, M Sekiguchi |
Japanese Circulation Journal | 1998 |
Measurement of heart rate and Q-T interval in the conscious mouse
GF Mitchell, A Jeron, G Koren |
American journal of physiology. Heart and circulatory physiology | 1998 |
Familial Hypertrophic Cardiomyopathy: From Mutations to Functional Defects
G Bonne, L Carrier, P Richard, B Hainque, K Schwartz |
Circulation research | 1998 |
Cardiac Physiology in Transgenic Mice
JF James, TE Hewett, J Robbins |
Circulation research | 1998 |
Cardiac Arrhythmias, Pacing & Electrophysiology
PE Vardas |
1998 | |
Molecular biology of human arrhythmias: implications for the clinical electrophysiologist
N A Estes 3rd, M E Mendelsohn |
Journal of Interventional Cardiac Electrophysiology | 1998 |
Familial hypertrophic cardiomyopathy mice display gender differences in electrophysiological abnormalities
C I Berul, M E Christe, M J Aronovitz, C T Maguire, C E Seidman, J G Seidman, M E Mendelsohn |
Journal of Interventional Cardiac Electrophysiology | 1998 |
Animal Models in Cardiovascular Research
DR Gross |
1985 |