Korean Circ J.  2003 Dec;33(12):1165-1173. 10.4070/kcj.2003.33.12.1165.

Cardiac Hypertrophy in Transgenic Mice with Overexpressed Small-Subunit of Human Myosin Light Chain Phosphatase

• Bae SW
• Lee WH
• Kim CH
• Park HK
• Lee SC
• Ko YH
• Park SW
• Arimura T
• Kimura A
• Park JE

• KMID: 2227250
• DOI: http://doi.org/10.4070/kcj.2003.33.12.1165

Abstract

BACKGROUND AND OBJECTIVES
Recent reports have demonstrated that perturbation of the balance between myo-sin light chain (MLC) phosphorylation and the dephosphorylation status is associated with the development of cardiac hypertrophy. Myosin light chain phosphatase (MLCP) is a key enzyme that regulates the phosphorylation status of the MLC, but its functional roles in cardiac muscle have not been well investigated. Especially, the functions of the small-subunit of MLCP in cardiac muscles are not well elucidated. Here, whether the human heart-specific small-subunit (M21) of MLCP is associated with hypertrophic responses in a transgenic mice model were assessed.
MATERIALS AND METHODS
The transgenic mice, overexpressing the human M21, were generated from a cardiac-specific transgenic construct. Cardiac tissues from the transgenic mice were subjected to histology for their morphological examination. The echocardiographic parameters of the murine heart were examined with transgenic mice aged 1, 2 and 3 months, and compared with their non-transgenic littermates. To determine whether the transgenic heart was sensitive to stress, the echocardiographic examination was also performed at the baseline, both before and after the administration of isoproterenol, at a dosage of 30 microgram/g/day, for 2 weeks.
RESULTS
The histological analysis of the transgenic heart revealed myocyte disarray and nuclear hypertrophy. No significant differences were observed between the transgenic and non-transgenic mice in relation to the echocardiographic determinants, such as the left ventricular dimensions and the wall thickness. Chronic cardiac stress, induced by isoproterenol infusion, also failed to show any significant differences in relation to the same determinants.
CONCLUSION
Overexpression of the human M21 in the murine heart induced myocyte hypertrophy. However, the overall cardiac functions were not affected under normal and stressed conditions.

Keyword

Cardiomyopathy, hypertrophic; Phosphatase, myosin light chain; Calcium sensitivity; Mice, transgenic; Protein subunits

MeSH Terms

Animals
Cardiomegaly*
Cardiomyopathy, Hypertrophic
Echocardiography
Heart
Humans*
Hypertrophy
Isoproterenol
Mice
Mice, Transgenic*
Muscle Cells
Myocardium
Myosin Light Chains*
Myosin-Light-Chain Phosphatase*
Myosins*
Phosphorylation
Protein Subunits
Isoproterenol
Myosin Light Chains
Myosin-Light-Chain Phosphatase
Myosins
Protein Subunits