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Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart.
Open accessAbstract
The alpha-myosin heavy chain (alpha-MyHC) is the major contractile protein expressed in the myocardium of adult mice. We have produced mice carrying a null mutation of alpha-MyHC by homologous recombination in murine ES cells. Homozygous null animals die between 11 and 12 d in utero of gross heart defects, while alpha-MyHC+/- heterozygotes survive and appear externally normal. The presence of a single functional alpha-MyHC+ allele in heterozygous animals results in reduced levels of the transcript and protein as well as fibrosis and alterations in sarcomeric structure. Examination of heart function using a working heart preparation revealed severe impairment of both contractility and relaxation in a subset of the alpha-MyHC+/- animals. Thus, two alpha-MyHC+ alleles are necessary for normal cardiac development, and hemizygosity for the normal allele can result in altered cardiac function.
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Citations
Cited by
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Bueno, O. F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.23.6341 · Cited by 774
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Murphy, A. M., Kögler, H., Georgakopoulos, D., McDonough, J. L., Kass, D. A., Van Eyk, J. E., & Marbán, E. (2000) · Science · doi:10.1126/science.287.5452.488 · Cited by 228
Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice
Reichart, D., Newby, G. A., Wakimoto, H., Lun, M., Gorham, J. M., Curran, J. J., Raguram, A., DeLaughter, D. M., Conner, D. A., Marsiglia, J. D. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-022-02190-7 · Cited by 203
Metadata
- Authors
- Jones, W. K., Grupp, I. L., Doetschman, T., Grupp, G., Osinska, H., Hewett, T. E., Boivin, G., Gulick, J., Ng, W. A., & Robbins, J.
- Venue
- Journal of Clinical Investigation
- Published
- 1996-10-15
- Volume
- 98
- Issue
- 8
- Pages
- 1906-1917
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2091163358
- Cited by
- 200
- References
- 0
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart. https://app.cochat.ai/papers/10.1172/jci118992
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- Jones, W. K., Grupp, I. L., Doetschman, T., Grupp, G., Osinska, H., Hewett, T. E., Boivin, G., Gulick, J., Ng, W. A., & Robbins, J. (1996). Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart. Journal of Clinical Investigation. https://doi.org/10.1172/jci118992
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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