In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 3 ( 2006-08-04), p. 323-331
Abstract:
Although it is well known that mutations in the cardiac regulatory myosin light chain-2 ( mlc-2 ) gene cause hypertrophic cardiomyopathy, the precise in vivo structural and functional roles of MLC-2 in the heart are only poorly understood. We have isolated a mutation in zebrafish, tell tale heart ( tel m225 ), which selectively perturbs contractility of the embryonic heart. By positional cloning, we identified tel to encode the zebrafish mlc-2 gene. In contrast to mammals, zebrafish have only 1 cardiac-specific mlc-2 gene, which we find to be expressed in atrial and ventricular cardiomyocytes during early embryonic development, but also in the adult heart. Accordingly, loss of zMLC-2 function cannot be compensated for by upregulation of another mlc-2 gene. Surprisingly, ultrastructural analysis of tel cardiomyocytes reveals complete absence of organized thick myofilaments. Thus, our findings provide the first in vivo evidence that cardiac MLC-2 is required for thick-filament stabilization and contractility in the vertebrate heart.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000234807.16034.fe
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2006
detail.hit.zdb_id:
1467838-X
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