The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure
Open accessAbstract
The structural integrity of the heart is maintained by the end-to-end connection between the myocytes called the intercalated disc. The intercalated disc contains different junctional complexes that enable the myocardium to function as a syncytium. One of the junctional complexes, the zonula adherens or adherens junction, consists of the cell adhesion molecule, N-cadherin, which mediates strong homophilic cell–cell adhesion via linkage to the actin cytoskeleton. To determine the function of N-cadherin in the working myocardium, we generated a conditional knockout containing loxP sites flanking exon 1 of the N-cadherin ( Cdh2 ) gene. Using a cardiac-specific tamoxifen-inducible Cre transgene, N-cadherin was deleted in the adult myocardium. Loss of N-cadherin resulted in disassembly of the intercalated disc structure, including adherens junctions and desmosomes. The mutant mice exhibited modest dilated cardiomyopathy and impaired cardiac function, with most animals dying within two months after tamoxifen administration. Decreased sarcomere length and increased Z-line thickness were observed in the mutant hearts consistent with loss of muscle tension because N-cadherin was no longer available to anchor myofibrils at the plasma membrane. Ambulatory electrocardiogram monitoring captured the abrupt onset of spontaneous ventricular tachycardia, confirming that the deaths were arrhythmic in nature. A significant decrease in the gap junction protein, connexin 43, was observed in the N-cadherin–depleted hearts. This animal model provides the first demonstration of the hierarchical relationship of the structural components of the intercalated disc in the working myocardium, thus establishing N-cadherin’s paramount importance in maintaining the structural integrity of the heart.
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Cites
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High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP
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Developmental Defects in Mouse Embryos Lacking N-Cadherin
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Self-citationSohal, D. S., Nghiem, M., Crackower, M. A., Witt, S. A., Kimball, T. R., Tymitz, K. M., Penninger, J. M., & Molkentin, J. D. (2001) · Circulation Research · doi:10.1161/hh1301.092687 · Cited by 695
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Structural correlate of atrial fibrillation in human patients
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Cited by
Kirchhof, P., Fabritz, L., Zwiener, M., Witt, H., Schäfers, M., Zellerhoff, S., Paul, M., Athai, T., Hiller, K.-H., Baba, H. A., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.624502 · Cited by 429
Multicellular spheroids in ovarian cancer metastases: Biology and pathology
Shield, K., Ackland, M. L., Ahmed, N., & Rice, G. E. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.11.032 · Cited by 412
N-cadherin mediates cortical organization in the mouse brain
Kadowaki, M., Nakamura, S., Machon, O., Krauss, S., Radice, G. L., & Takeichi, M. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2006.12.014 · Cited by 301
Self-citationLi, J., Patel, V. V., Kostetskii, I., Xiong, Y., Chu, A. F., Jacobson, J. T., Yu, C., Morley, G. E., Molkentin, J. D., & Radice, G. L. (2005) · Circulation Research · doi:10.1161/01.res.0000181132.11393.18 · Cited by 223
Self-citationNiche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem Cells
Goel, A. J., Rieder, M.-K., Arnold, H.-H., Radice, G. L., & Krauss, R. S. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.102 · Cited by 146
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Metadata
- Authors
- Kostetskii, I., Li, J., Xiong, Y., Zhou, R., Ferrari, V. A., Patel, V. V., Molkentin, J. D., & Radice, G. L.
- Venue
- Circulation Research
- Published
- 2005-02-18
- Volume
- 96
- Issue
- 3
- Pages
- 346-354
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2118567467
- Cited by
- 331
- References
- 38
- FWCI
- 14.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure. https://app.cochat.ai/papers/10.1161/01.res.0000156274.72390.2c
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- Kostetskii, I., Li, J., Xiong, Y., Zhou, R., Ferrari, V. A., Patel, V. V., Molkentin, J. D., & Radice, G. L. (2005). Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure. Circulation Research. https://doi.org/10.1161/01.res.0000156274.72390.2c
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
