Recent progresses in signal transduction have revealed that β-catenin signaling controls embryonic development, tumorigenesis, cell shape, and polarity. The role of this pathway in myocyte shape regulation during cardiac hypertrophy and failure is, however, not clearly defined. Since homozygous knockout of β-catenin is embryonically lethal, we have deleted β-catenin genes specifically in the heart of adult mice by crossing loxP-flanked β-catenin mice with transgenic mice expressing tamoxifen-activated MerCreMer protein (MCM) driven by the α-myosin heavy chain promoter. Administration of tamoxifen to homozygous loxP-flanked β-catenin mice positive for MCM induces the deletion of β-catenin only in cardiomyocytes. Immunolabeling with β-catenin antibody demonstrates that 90% of cardiomyocytes completely lose their β-catenin expression but maintain normal rod-shaped morphology. The intercalated disk of cardiomyocytes lacking β-catenin is morphologically unremarkable with normal distribution of vinculin, N-cadherin, desmoplakin, ZO-1, connexin43, and α-, γ-, and p120 catenins. The expression level of these proteins, except that of γ-catenin, is also similar in tamoxifen-treated and control mice with both homozygous loxP-flanked β-catenin genes and the MCM transgene. Western blot analyses reveal that γ-catenin increases in the heart of β-catenin knockout mice compared with controls. Confocal microscopy also demonstrates that γ-catenin has significantly increased in the intercalated disk of cardiomyocytes lacking β-catenin. Echocardiographic data indicate that the knockout mice maintain normal ventricular geometry and cardiac function. The results suggest that upregulation of γ-catenin can compensate for the loss of β-catenin in cardiomyocytes to maintain normal cardiac structure and function.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Jan 2007|
- Intercalated disk
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)