Upregulation of γ-catenin compensates for the loss of β-catenin in adult cardiomyocytes

作者：Jibin Zhou, Jiaxiang Qu, Xian Ping Yi, Kelly Graber, Lu Huber, Xuejun Wang, A. Martin Gerdes, Faqian Li · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2006 · DOI：10.1152/ajpheart.00576.2006 · 被引用次数：75 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation、Cardiovascular Effects of Exercise

Recent progresses in signal transduction have revealed that beta-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 beta-catenin is embryonically lethal, we have deleted beta-catenin genes specifically in the heart of adult mice by crossing loxP-flanked beta-catenin mice with transgenic mice expressing tamoxifen-activated MerCreMer protein (MCM) driven by the alpha-myosin heavy chain promoter. Administration of tamoxifen to homozygous loxP-flanked beta-catenin mice positive for MCM induces the deletion of beta-catenin only in cardiomyocytes. Immunolabeling with beta-catenin antibody demonstrates that 90% of cardiomyocytes completely lose their beta-catenin expression but maintain normal rod-shaped morphology. The intercalated disk of cardiomyocytes lacking beta-catenin is morphologically unremarkable with normal distribution of vinculin, N-cadherin, desmoplakin, ZO-1, connexin43, and alpha-, gamma-, and p120 catenins. The expression level of these proteins, except that of gamma-catenin, is also similar in tamoxifen-treated and control mice with both homozygous loxP-flanked beta-catenin genes and the MCM transgene. Western blot analyses reveal that gamma-catenin increases in the heart of beta-catenin knockout mice compared with controls. Confocal microscopy also demonstrates that gamma...