Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice. Agostino A et al. (2003) 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.//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: unknown
Comment: SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Zhu Z et al. (1998) Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. COX deficiency is an autosomal recessive trait and most patients belong to a single genetic complementation group. DNA sequence analysis of the genes encoding the structural subunits of the COX complex has failed to identify a pathogenic mutation. Using microcell-mediated chromosome transfer, we mapped the gene defect in this disorder to chromosome 9q34 by complementation of the respiratory chain deficiency in patient fibroblasts. Analysis of a candidate gene (SURF1) of unknown function revealed several mutations, all of which predict a truncated protein. These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.//////////////////