Myh7-KO Mouse

Myh7, also known as myosin heavy chain 7, is a sarcomeric gene encoding the myosin heavy chain (myosin-7). It plays fundamental functions in cardiac and skeletal muscle contraction [1]. The gene is associated with pathways related to muscle contraction and is of great biological importance in understanding muscle-related diseases. Genetic models, such as in vivo and in vitro models, are valuable for studying Myh7.

Mutations in Myh7 are closely related to cardiomyopathy and skeletal muscle myopathy [1]. In cardiomyopathy, Myh7-related dilated cardiomyopathy is characterized by early age of onset, high phenotypic expression, low left-ventricular reverse remodeling, and frequent progression to end-stage heart failure, with heart failure complications being more common than ventricular arrhythmias [2]. For hypertrophic cardiomyopathy, different types of variants in Myh7 have distinct effects. For example, the incomplete-penetrant MYH7 G256E mutation causes hypercontractility and elevated mitochondrial respiration [3]. MYH7-related HCM shows a lower long-term prevalence of systolic dysfunction compared with MYBPC3-related HCM [4]. Also, the MYH7 R453C mutation can induce cardiac remodeling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways [5]. In terms of myopathy, recessive Myh7 mutations are rare but can cause myopathy with features like infancy/childhood onset, axial/proximal weakness, spinal rigidity, severe scoliosis, and progressive respiratory impairment [6]. Additionally, Myh7 variants are associated with complex congenital heart disease, expanding the phenotypic spectrum of Myh7-related cardiac diseases [7].

In conclusion, Myh7 is essential for muscle contraction in both cardiac and skeletal muscles. Model-based research, including in vivo studies, has revealed its role in various muscle-related diseases such as cardiomyopathy, skeletal muscle myopathy, and congenital heart disease. Understanding Myh7 contributes to a better understanding of the mechanisms underlying these diseases and may provide potential directions for treatment.

References:

1. Gao, Yuan, Peng, Lu, Zhao, Cuifen. 2023. MYH7 in cardiomyopathy and skeletal muscle myopathy. In Molecular and cellular biochemistry, 479, 393-417. doi:10.1007/s11010-023-04735-x. https://pubmed.ncbi.nlm.nih.gov/37079208/

2. de Frutos, Fernando, Ochoa, Juan Pablo, Navarro-Peñalver, Marina, Elliot, Perry M, Garcia-Pavia, Pablo. 2022. Natural History of MYH7-Related Dilated Cardiomyopathy. In Journal of the American College of Cardiology, 80, 1447-1461. doi:10.1016/j.jacc.2022.07.023. https://pubmed.ncbi.nlm.nih.gov/36007715/

3. Lee, Soah, Vander Roest, Alison S, Blair, Cheavar A, Spudich, James A, Bernstein, Daniel. 2024. Incomplete-penetrant hypertrophic cardiomyopathy MYH7 G256E mutation causes hypercontractility and elevated mitochondrial respiration. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2318413121. doi:10.1073/pnas.2318413121. https://pubmed.ncbi.nlm.nih.gov/38683993/

4. Beltrami, Matteo, Fedele, Elisa, Fumagalli, Carlo, Poggesi, Corrado, Olivotto, Iacopo. 2023. Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy. In Circulation. Genomic and precision medicine, 16, 363-371. doi:10.1161/CIRCGEN.122.003832. https://pubmed.ncbi.nlm.nih.gov/37409452/

5. Wang, Lingyu, Li, Linquan, Zhao, Dazhong, Lu, Yi, Ouyang, Hongsheng. 2024. MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways. In Open biology, 14, 230427. doi:10.1098/rsob.230427. https://pubmed.ncbi.nlm.nih.gov/38862020/

6. Beecroft, Sarah J, van de Locht, Martijn, de Winter, Josine M, McLean, Catriona A, Jungbluth, Heinz. 2019. Recessive MYH7-related myopathy in two families. In Neuromuscular disorders : NMD, 29, 456-467. doi:10.1016/j.nmd.2019.04.002. https://pubmed.ncbi.nlm.nih.gov/31130376/

7. Ritter, Alyssa, Leonard, Jacqueline, Gray, Christopher, Owens, Anjali, Ahrens-Nicklas, Rebecca C. 2022. MYH7 variants cause complex congenital heart disease. In American journal of medical genetics. Part A, 188, 2772-2776. doi:10.1002/ajmg.a.62766. https://pubmed.ncbi.nlm.nih.gov/35491958/