Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency

• Published in: Human molecular genetics 2005-09, Vol.14 (18), p.2737-2748
• Main Authors: Diaz, Francisca, Thomas, Christine K., Garcia, Sofia, Hernandez, Dayami, Moraes, Carlos T.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cloning, Molecular; Crosses, Genetic; Cytochrome-c Oxidase Deficiency - genetics; Disease Models, Animal; Disease Progression; Electron Transport Complex IV - genetics; Fundamental and applied biological sciences. Psychology; Gene Transfer Techniques; Genetics of eukaryotes. Biological and molecular evolution; Immunohistochemistry; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Mitochondrial Myopathies - genetics; Molecular and cellular biology; Molecular Probe Techniques; Muscle Fatigue - genetics; Muscle, Skeletal - metabolism; Muscle, Skeletal - ultrastructure; Mutation, Missense - genetics
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddi307

We have created a mouse model with an isolated cytochrome c oxidase (COX) deficiency by disrupting the COX10 gene in skeletal muscle. Missense mutations in COX10 have been previously associated with mitochondrial disorders. Cox10p is a protoheme:heme-O-farnesyl transferase required for the synthesis of heme a, the prosthetic group of the catalytic center of COX. COX10 conditional knockout mice were generated by crossing a LoxP-tagged COX10 mouse with a transgenic mouse expressing cre recombinase under the myosin light chain 1f promoter. The COX10 knockout mice were healthy until approximately 3 months of age when they started developing a slowly progressive myopathy. Surprisingly, even though COX activity in COX10 KO muscles was