| Autor: |
Gustafson-Wagner, Elisabeth A., Sinn, Haley W., Yen-Lin Chen, Da-Zhi Wang, Reiter, Rebecca S., Lin, Jenny L.-C., Baoli Yang, Williamson, Roger A., Ju Chen, Lin, Cheng-I., Lin, Jim J.-C. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Nov2007, Vol. 293 Issue 5, pH2680-H2692, 13p, 1 Chart, 11 Graphs |
| Abstrakt: |
The intercalated disk protein Xin was originally discovered in chicken striated muscle and implicated in cardiac morphogenesis. In the mouse, there are two homologous genes, mXinα and mXinβ. The human homolog of mXinα, Cmya1, maps to chromosomal region 3p21.2-21.3, near a dilated cardiomyopathy with conduction defect-2 locus. Here we report that mXinα-null mouse hearts are hypertrophied and exhibit fibrosis, indicative of cardiomyopathy. A significant upregulation of mXinβ likely provides partial compensation and accounts for the viability of the mXinα-null mice. Ultrastructural studies of mXinα-null mouse hearts reveal intercalated disk disruption and myofilament disarray. In mXinα-null mice, there is a significant decrease in the expression level of p120-catenin, β-catenin, N-cadherin, and desmoplakin, which could compromise the integrity of the intercalated disks and functionally weaken adhesion, leading to cardiac defects. Additionally, altered localization and decreased expression of connexin 43 are observed in the mXinα-null mouse heart, which, together with previously observed abnormal electrophysiological properties of mXinα-deficient mouse ventricular myocytes, could potentially lead to conduction defects. Indeed, ECG recordings on isolated, perfused hearts (Langendorff preparations) show a significantly prolonged QT interval in mXinα-deficient hearts. Thus mXinα functions in regulating the hypertrophic response and maintaining the structural integrity of the intercalated disk in normal mice, likely through its association with adherens junctional components and actin cytoskeleton. The mXinα-knockout mouse line provides a novel model of cardiac hypertrophy and cardiomyopathy with conduction defects. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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