scholarly journals Effects of Total Replacement of Atrial Myosin Light Chain-2 With the Ventricular Isoform in Atrial Myocytes of Transgenic Mice

Circulation ◽  
1998 ◽  
Vol 97 (15) ◽  
pp. 1508-1513 ◽  
Author(s):  
Corinn M. Pawloski-Dahm ◽  
Guojie Song ◽  
Darryl L. Kirkpatrick ◽  
Joe Palermo ◽  
James Gulick ◽  
...  
1994 ◽  
Vol 269 (24) ◽  
pp. 16961-16970
Author(s):  
S.W. Kubalak ◽  
W.C. Miller-Hance ◽  
T.X. O'Brien ◽  
E. Dyson ◽  
K.R. Chien

1988 ◽  
Vol 8 (2) ◽  
pp. 1006-1009 ◽  
Author(s):  
M Shani ◽  
I Dekel ◽  
O Yoffe

The expression of the rat skeletal myosin light-chain 2 gene in two transgenic strains was tissue specific and stage specific. However, the temporal regulation during development of the transgene was different from that of the endogenous gene. Surprisingly, in one strain, the expression of the transgene was associated with a significant down-regulation of the endogenous gene. The possible mechanisms to account for the suppression of the endogenous gene and the potential implications of this suppression are discussed.


2018 ◽  
Vol 314 (6) ◽  
pp. H1192-H1202 ◽  
Author(s):  
Takuro Arimura ◽  
Antoine Muchir ◽  
Masayoshi Kuwahara ◽  
Sachio Morimoto ◽  
Taisuke Ishikawa ◽  
...  

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21 transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21 results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation. NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.


2000 ◽  
Vol 90 (3-4) ◽  
pp. 248-252 ◽  
Author(s):  
P.A. Doevendans ◽  
R. Bronsaer ◽  
P.R. Lozano ◽  
S. Kubalak ◽  
M. van Bilsen

1988 ◽  
Vol 8 (2) ◽  
pp. 1006-1009
Author(s):  
M Shani ◽  
I Dekel ◽  
O Yoffe

The expression of the rat skeletal myosin light-chain 2 gene in two transgenic strains was tissue specific and stage specific. However, the temporal regulation during development of the transgene was different from that of the endogenous gene. Surprisingly, in one strain, the expression of the transgene was associated with a significant down-regulation of the endogenous gene. The possible mechanisms to account for the suppression of the endogenous gene and the potential implications of this suppression are discussed.


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