Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice
| Autor: | Alessandro Prelle, Massimo Zeviani, Valeria Tiranti, Cecilia Tiveron, Alessio Giavazzi, Federica Invernizzi, Alessandro Agostino, Eleonora Lamantea, Giorgio Battaglia, Laura Tatangelo, Gigliola Fagiolari |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Mitochondrial Diseases Time Factors Cytochrome-c Oxidase Deficiency Mitochondrion Pathogenesis Mice Models SURF1 Tissue Distribution Southern Genetics (clinical) Genetics Mice Knockout Blotting Reverse Transcriptase Polymerase Chain Reaction Brain General Medicine Skeletal Phenotype Immunohistochemistry Blotting Southern medicine.anatomical_structure Liver Alleles Animals Blotting Western Electron Transport Complex IV Electrophoresis Polyacrylamide Gel Female Genetic Vectors Humans Immunoblotting Membrane Proteins Mitochondrial Proteins Models Genetic Muscle Skeletal Proteins Knockout mouse Muscle Western Electrophoresis Mitochondrial disease Knockout Biology Genetic medicine Cytochrome c oxidase Molecular Biology Polyacrylamide Gel Skeletal muscle medicine.disease Molecular biology biology.protein |
| Zdroj: | Human molecular genetics. 12(4) |
| ISSN: | 0964-6906 |
| Popis: | We report here the creation of a constitutive knockout mouse for SURF1, a gene encoding one of the assembly proteins involved in the formation of cytochrome c oxidase (COX). Loss-of-function mutations of SURF1 cause Leigh syndrome associated with an isolated and generalized COX deficiency in humans. The murine phenotype is characterized by the following hallmarks: (1) high post-implantation embryonic lethality, affecting approximately 90% of the Surf1(-/-) individuals; (2) early-onset mortality of post-natal individuals; (3) highly significant deficit in muscle strength and motor performance; (4) profound and isolated defect of COX activity in skeletal muscle and liver, and, to a lesser extent, heart and brain; (5) morphological abnormalities of skeletal muscle, characterized by reduced histochemical reaction to COX and mitochondrial proliferation; (6) no obvious abnormalities in brain morphology, reflecting the virtual absence of overt neurological symptoms. These results indicate a function for murine Surf1 protein (Surf1p) specifically related to COX and recapitulate, at least in part, the human phenotype. This is the first mammalian model for a nuclear disease gene of a human mitochondrial disorder. Our model constitutes a useful tool to investigate the function of Surf1p, help understand the pathogenesis of Surf1p deficiency in vivo, and evaluate the efficacy of treatment. |
| Databáze: | OpenAIRE |
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