Loss of mXinα, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects

Elisabeth A Gustafson-Wagner; Haley W Sinn; Yen-Lin Chen; Da-Zhi Wang; Rebecca S Reiter; Jenny L.-C Lin; Baoli Yang; Roger A Williamson; Ju Chen; Cheng-I Lin; Jim J.-C Lin

doi:10.1152/ajpheart.00806.2007

Back

Loss of mXinα, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects

Journal article

Open access

Loss of mXinα, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects

Elisabeth A Gustafson-Wagner, Haley W Sinn, Yen-Lin Chen, Da-Zhi Wang, Rebecca S Reiter, Jenny L.-C Lin, Baoli Yang, Roger A Williamson, Ju Chen, Cheng-I Lin, …

American Journal of Physiology (Consolidated), Vol.293(5), p.H2680

11/01/2007

DOI: 10.1152/ajpheart.00806.2007

PMCID: PMC2394510

PMID: 17766470

Files and links (1)

url

https://doi.org/10.1152/ajpheart.00806.2007View

Published (Version of record) Open Access

Abstract

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[alpha] and toxin[beta]. The human homolog of mXin[alpha], Cmya1, maps to chromosomal region 3p21.2-21.3, near a dilated cardiomyopathy with conduction defect-2 locus. Here we report that mXin[alpha]-null mouse hearts are hypertrophied and exhibit fibrosis, indicative of cardiomyopathy. A significant upregulation of mXin[beta] likely provides partial compensation and accounts for the viability of the mXin[alpha]-null mice. Ultrastructural studies of mXin[alpha]-null mouse hearts reveal intercalated disk disruption and myofilament disarray. In mXin[alpha]-null mice, there is a significant decrease in the expression level of p120-catenin, [beta]-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[alpha]-null mouse heart, which, together with previously observed abnormal electrophysiological properties of mXin[alpha]-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[alpha]-deficient hearts. Thus mXin[alpha] 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[alpha]-knockout mouse line provides a novel model of cardiac hypertrophy and cardiomyopathy with conduction defects.

Cardiomyopathy

Heart Diseases

Causes of

Physiological research

Heart enlargement

Details

Title: Subtitle: Loss of mXinα, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects
Creators: Elisabeth A Gustafson-Wagner
Haley W Sinn
Yen-Lin Chen
Da-Zhi Wang
Rebecca S Reiter
Jenny L.-C Lin
Baoli Yang
Roger A Williamson - University of Iowa, Obstetrics and Gynecology
Ju Chen
Cheng-I Lin
Jim J.-C Lin
Resource Type: Journal article
Publication Details: American Journal of Physiology (Consolidated), Vol.293(5), p.H2680
DOI: 10.1152/ajpheart.00806.2007
PMID: 17766470
PMCID: PMC2394510
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Publisher: American Physiological Society
Language: English
Date published: 11/01/2007
Description audience: Academic
Academic Unit: Biology; Obstetrics and Gynecology
Record Identifier: 9983557784602771

Metrics

14 Record Views

58 Times Cited - Web of Science