Molecular remodeling of cardiac contractile function

被引:30
作者
James, J [1 ]
Robbins, J [1 ]
机构
[1] CHILDRENS HOSP, DEPT PEDIAT, DIV MOL CARDIOVASC BIOL, RES FDN, CINCINNATI, OH 45229 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1997年 / 273卷 / 05期
关键词
contractile proteins; genetics; transgenic; gene targeting;
D O I
10.1152/ajpheart.1997.273.5.H2105
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A number of techniques are now available that allow the contractile apparatus of the heart to be altered in a defined manner. This review focuses on those approaches that result in germ-line transmission of the remodeling event(s). Thus the desired modifications can be propagated stably throughout multiple generations and result in the creation of stable, new animal models. Necessarily, such stable changes need to be performed at the level of the genome, and two distinct but complementary approaches have been developed: transgenesis and gene targeting. Each results in the stable modification of the mammalian genome. Via gene targeting or gene ablation of sequences encoding various components of the sarcomere, the contractile apparatus of the heart can be altered dramatically. Ablating a gene may lead to a loss in function, which can help establish a function of the candidate sequence. Gene targeting can also be used to effect changes in the sequences encoding a functional domain of the contractile protein or at a single-amino acid residue, resulting in the establishment of precise structure-function relationships. With the use of transgenesis, the contractile apparatus of the heart can also be significantly remodeled. These approaches are rapidly creating a group of animals in which altered contractile protein complements will lead to a fundamental understanding of the structure-function relationships that underlie the function of the heart at the molecular, biochemical, whole organ, and whole animal levels.
引用
收藏
页码:H2105 / H2118
页数:14
相关论文
共 118 条
  • [1] Gene recombination in postmitotic cells - Targeted expression of cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo
    Agah, R
    Frenkel, PA
    French, BA
    Michael, LH
    Overbeek, PA
    Schneider, MD
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (01) : 169 - 179
  • [2] MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure
    Arber, S
    Hunter, JJ
    Ross, J
    Hongo, M
    Sansig, G
    Borg, J
    Perriard, JC
    Chien, KR
    Caroni, P
    [J]. CELL, 1997, 88 (03) : 393 - 403
  • [3] SITE-DIRECTED POINT MUTATIONS IN EMBRYONIC STEM-CELLS - A GENE-TARGETING TAG-AND-EXCHANGE STRATEGY
    ASKEW, GR
    DOETSCHMAN, T
    LINGREL, JB
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (07) : 4115 - 4124
  • [4] CONTRACTILE PROTEIN ISOFORMS IN MUSCLE DEVELOPMENT
    BANDMAN, E
    [J]. DEVELOPMENTAL BIOLOGY, 1992, 154 (02) : 273 - 283
  • [5] BARANY M, 1967, SCIENCE, V231, P597
  • [6] BARR E, 1994, GENE THER, V1, P51
  • [7] Strategies for studying cardiovascular phenotypes in genetically manipulated mice
    Becker, KD
    Gottshall, KR
    Chien, KR
    [J]. HYPERTENSION, 1996, 27 (03) : 495 - 501
  • [8] BERNSTEIN SI, 1993, INT REV CYTOL, V143, P63
  • [9] ALTERATIONS IN CARDIAC GENE-EXPRESSION DURING THE TRANSITION FROM STABLE HYPERTROPHY TO HEART-FAILURE - MARKED UP-REGULATION OF GENES ENCODING EXTRACELLULAR-MATRIX COMPONENTS
    BOLUYT, MO
    ONEILL, L
    MEREDITH, AL
    BING, OHL
    BROOKS, WW
    CONRAD, CH
    CROW, MT
    LAKATTA, EG
    [J]. CIRCULATION RESEARCH, 1994, 75 (01) : 23 - 32
  • [10] Single-copy transgenic mice with chosen-site integration
    Bronson, SK
    Plaehn, EG
    Kluckman, KD
    Hagaman, JR
    Maeda, N
    Smithies, O
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (17) : 9067 - 9072