{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:45:01Z","timestamp":1792665901008,"version":"4.5.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>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, mXin\u03b1 and mXin\u03b2. The human homolog of mXin\u03b1, Cmya1, maps to chromosomal region 3p21.2\u201321.3, near a dilated cardiomyopathy with conduction defect-2 locus. Here we report that mXin\u03b1-null mouse hearts are hypertrophied and exhibit fibrosis, indicative of cardiomyopathy. A significant upregulation of mXin\u03b2 likely provides partial compensation and accounts for the viability of the mXin\u03b1-null mice. Ultrastructural studies of mXin\u03b1-null mouse hearts reveal intercalated disk disruption and myofilament disarray. In mXin\u03b1-null mice, there is a significant decrease in the expression level of p120-catenin, \u03b2-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 mXin\u03b1-null mouse heart, which, together with previously observed abnormal electrophysiological properties of mXin\u03b1-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 mXin\u03b1-deficient hearts. Thus mXin\u03b1 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 mXin\u03b1-knockout mouse line provides a novel model of cardiac hypertrophy and cardiomyopathy with conduction defects.<\/jats:p>","DOI":"10.1152\/ajpheart.00806.2007","type":"journal-article","created":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:54:49Z","timestamp":1188608089000},"page":"H2680-H2692","source":"Crossref","is-referenced-by-count":59,"title":["Loss of mXin\u03b1, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects"],"prefix":"10.1152","volume":"293","author":[{"given":"Elisabeth A.","family":"Gustafson-Wagner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley W.","family":"Sinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Zhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny L.-C.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A.","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-I.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim J.-C.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00628-4"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81878-4"},{"key":"R3","unstructured":"Cheng CP, Loh YX, Lin CI, Lai YJ, Chen YC, Sytwu HK, Gustafson-Wagner EA, Lin JJC.Electrophysiological characteristics of ventricular myocytes of Xin\u03b1-deficient mice. 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