Cardiac electrophysiology in genetically engineered mice

被引:44
作者
Gehrmann, J [1 ]
Berul, CI [1 ]
机构
[1] Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA
关键词
ex vivo electrophysiology; in vivo electrophysiology; mice; molecular biology; functional genomics; animal model;
D O I
10.1111/j.1540-8167.2000.tb01806.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mouse Electrophysiology. The mouse has become the principal animal model for studying biologic processes in mammals. Major advances in transgene and gene targeting technology enabled manipulation of the mouse genome in a predictable fashion. Mutant mouse strains provide important insights into the molecular mechanisms underlying normal and disordered cardiac conduction and sudden cardiac death. A variety of mouse strains harboring gene mutations leading to inherited developmental disorders have been designed. Structural protein abnormalities, connexin protein defects, and ion channelopathies associated with human clinical phenotypes, including congenital heart disease, cardiomyopathies, long QT syndrome, and muscular dystrophy, have been engineered into the mouse genome, creating models of human electrophysiologic disease. Functional analyses of the underlying molecular mechanisms of resultant phenotypes require appropriate and sophisticated experimental methodology. In this review, genetic mouse models pertinent to human arrhythmogenic disorders and their application to present-day ex vivo and in vivo murine electrophysiologic technology at the whole organ and animal levels are discussed.
引用
收藏
页码:354 / 368
页数:15
相关论文
共 113 条
  • [1] Mechanisms of disease - Ion channels - Basic science and clinical disease
    Ackerman, MJ
    Clapham, DE
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (22) : 1575 - 1586
  • [2] Baker LC, 1998, CIRCULATION, V98, P744
  • [3] An action plan for mouse genomics
    Battey, J
    Jordan, E
    Cox, D
    Dove, W
    [J]. NATURE GENETICS, 1999, 21 (01) : 73 - 75
  • [4] Bazett HC, 1920, HEART-J STUD CIRC, V7, P353
  • [5] Reduced penetrance, variable expressivity, and genetic heterogeneity of familial atrial septal defects
    Benson, DW
    Sharkey, A
    Fatkin, D
    Lang, P
    Basson, CT
    McDonough, B
    Strauss, AW
    Seidman, JG
    Seidman, CE
    [J]. CIRCULATION, 1998, 97 (20) : 2043 - 2048
  • [6] Electrophysiological abnormalities and arrhythmias in alpha MHC mutant familial hypertrophic cardiomyopathy mice
    Berul, CI
    Christe, ME
    Aronovitz, MJ
    Seidman, CE
    Seidman, JG
    Mendelsohn, ME
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (04) : 570 - 576
  • [7] USE OF THE RATE-CORRECTED JT INTERVAL FOR PREDICTION OF REPOLARIZATION ABNORMALITIES IN CHILDREN
    BERUL, CI
    SWEETEN, TL
    DUBIN, AM
    SHAH, MJ
    VETTER, VL
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1994, 74 (12) : 1254 - 1257
  • [8] Berul CI, 1999, CIRCULATION, V100, P207
  • [9] DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model
    Berul, CI
    Maguire, CT
    Aronovitz, MJ
    Greenwood, J
    Miller, C
    Gehrmann, J
    Housman, D
    Mendelsohn, ME
    Reddy, S
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (04) : R1 - R7
  • [10] In vivo cardiac electrophysiology studies in the mouse
    Berul, CI
    Aronovitz, MJ
    Wang, PJ
    Mendelsohn, ME
    [J]. CIRCULATION, 1996, 94 (10) : 2641 - 2648