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Publication type: Journal Article
Document type: Full Paper

Year: 1993

Author(s): Franz, WM; Breves, D; Klingel, K; Brem, G; Hofschneider, PH; Kandolf, R

Title: Heart-specific targeting of firefly luciferase by the myosin light chain-2 promoter and developmental regulation in transgenic mice.

Source: Circ Res (73), 4 629-638.

Authors Vetmeduni Vienna:

Brem Gottfried

Based on hybridization studies indicating constitutive expression levels of the endogenous myosin light chain-2 (MLC-2) gene in embryonic, fetal, and adult myocardium, a model system for selective targeting of genes to the heart of transgenic mice has been developed. A 2.1-kb DNA fragment of the 5' flanking region of the rat cardiac MLC-2 gene was fused to the firefly luciferase reporter gene and introduced into fertilized mouse oocytes. In four independent transgenic mouse lines, the expression of the MLC-2-luciferase fusion gene was found exclusively in heart muscle. In contrast to the endogenous MLC-2 gene, no luciferase activity was detectable in slow-twitch skeletal muscle or any other tissue of transgenic mice. This result suggests that the 2.1-kb DNA fragment of the 5' flanking region of the cardiac MLC-2 gene contains the regulatory elements required for selective gene expression in cardiac myocytes in vivo. In contrast to the endogenous steady-state MLC-2 expression during development, transgenic luciferase activity was 10-fold higher during embryogenesis, when formation of the ventricular loop and septum takes place. The enhanced luciferase activity in early heart development may suggest a growth-dependent control mechanism, involving either transcriptional or posttranscriptional regulation. In conclusion, this model system with the 2.1-kb ventricle-specific MLC-2 promoter sequence should facilitate the overexpression of gene products in the developing and mature heart muscle and further elucidate molecular mechanisms of myocardial diseases such as cardiomyopathies.

Keywords Pubmed: Animals - : Animals, Newborn - : Base Sequence - : Beetles - : Fetal Heart - metabolism : Gene Expression Regulation - metabolism : Heart - embryology : Luciferases - genetics : Mice - genetics : Mice, Transgenic - genetics : Molecular Sequence Data - genetics : Myocardium - metabolism : Myosins - genetics : Organ Specificity - genetics : Promoter Regions, Genetic - genetics : RNA, Messenger - analysis

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