1. Mutant myocilin impacts sarcomere ultrastructure in mouse gastrocnemius muscle
- Author
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Chuanxi Xiang, Ganesh Prasanna, Samir Reda, Bing Li, Andrew Dolman, Chenying Guo, Katie Dolan, and Jeffrey M. Lynch
- Subjects
0301 basic medicine ,Male ,Eye Diseases ,genetic structures ,Mutant ,Muscle Proteins ,Gene Expression ,lcsh:Medicine ,Sarcomere ,Biochemistry ,Mice ,0302 clinical medicine ,Nerve Fibers ,Myofibrils ,Animal Cells ,Medicine and Health Sciences ,lcsh:Science ,Musculoskeletal System ,Neurons ,Multidisciplinary ,Muscles ,Genetically Modified Organisms ,Gastrocnemius Muscles ,Animal Models ,Recombinant Proteins ,Cell biology ,medicine.anatomical_structure ,Phenotype ,Experimental Organism Systems ,Engineering and Technology ,Female ,Anatomy ,Cellular Types ,Genetic Engineering ,Glaucoma, Open-Angle ,Research Article ,Biotechnology ,Genetically modified mouse ,Sarcomeres ,Muscle Tissue ,Bioengineering ,Mouse Models ,Mice, Transgenic ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Gastrocnemius muscle ,Ciliary body ,Model Organisms ,Microscopy, Electron, Transmission ,Trabecular Meshwork ,medicine ,Animals ,Humans ,Eye Proteins ,Muscle, Skeletal ,Myocilin ,Intraocular Pressure ,Glycoproteins ,Muscle Cells ,Genetically Modified Animals ,Myocardium ,lcsh:R ,Skeletal muscle ,Biology and Life Sciences ,Proteins ,Glaucoma ,Cell Biology ,Axons ,Mice, Mutant Strains ,eye diseases ,Ophthalmology ,Cytoskeletal Proteins ,Disease Models, Animal ,030104 developmental biology ,Biological Tissue ,Skeletal Muscles ,Cellular Neuroscience ,Mutation ,030221 ophthalmology & optometry ,Animal Studies ,Mutant Proteins ,lcsh:Q ,Trabecular meshwork ,sense organs ,Neuroscience - Abstract
Myocilin (MYOC) is the gene with mutations most common in glaucoma. In the eye, MYOC is in trabecular meshwork, ciliary body, and retina. Other tissues with high MYOC transcript levels are skeletal muscle and heart. To date, the function of wild-type MYOC remains unknown and how mutant MYOC causes high intraocular pressure and glaucoma is ambiguous. By investigating mutant MYOC in a non-ocular tissue we hoped to obtain novel insight into mutant MYOC pathology. For this study, we utilized a transgenic mouse expressing human mutant MYOC Y437H protein and we examined its skeletal (gastrocnemius) muscle phenotype. Electron micrographs showed that sarcomeres in the skeletal muscle of mutant CMV-MYOC-Y437H mice had multiple M-bands. Western blots of soluble muscle lysates from transgenics indicated a decrease in two M-band proteins, myomesin 1 (MYOM1) and muscle creatine kinase (CKM). Immunoprecipitation identified CKM as a MYOC binding partner. Our results suggest that binding of mutant MYOC to CKM is changing sarcomere ultrastructure and this may adversely impact muscle function. We speculate that a person carrying the mutant MYOC mutation will likely have a glaucoma phenotype and may also have undiagnosed muscle ailments or vice versa, both of which will have to be monitored and treated.
- Published
- 2018