Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase
Copyright policy )Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase
Sod2-/- mice, which are deficient in the mitochondrial form of superoxide dismutase (MnSOD), have a short survival time that is strongly affected by genetic background. This suggests the existence of genetic modifiers that are capable of modulating the degree of mitochondrial oxidative damage caused by the MnSOD deficiency, thereby altering longevity. To identify these modifier(s), we generated recombinant congenic mice with quantitative trait loci (QTL) containing the putative genetic modifiers on the short-lived C57BL/6J genetic background. MnSOD deficient C57BL/6J mice with a QTL from the distal region of chromosome 13 from DBA/2J were able to survive for as long as those generated on the long-lived DBA/2J background. Within this region, the gene encoding nicotinamide nucleotide transhydrogenase (Nnt) was found to be defective in C57BL/6J mice, and no mature NNT protein could be detected. The forward reaction of NNT, a nuclear-encoded mitochondrial inner membrane protein, couples the generation of NADPH to proton transport and provides NADPH for the regeneration of two important antioxidant compounds, glutathione and thioredoxin, in the mitochondria. This action of NNT could explain its putative protective role in MnSOD-deficient mice.
- University of California, San Francisco United States
- Stanford University United States
- VA Palo Alto Health Care System United States
- Department of Pediatrics University of California San Diego United States
- Scripps Research Institute United States
Cell Nucleus, Male, Models, Genetic, Superoxide Dismutase, Quantitative Trait Loci, Mice, Inbred Strains, Models, Biological, Linkage Disequilibrium, Mitochondria, Mice, Inbred C57BL, Mice, Mice, Congenic, Phenotype, Mice, Inbred DBA, Mutation, NADP Transhydrogenases, Animals, Female, Alleles
Cell Nucleus, Male, Models, Genetic, Superoxide Dismutase, Quantitative Trait Loci, Mice, Inbred Strains, Models, Biological, Linkage Disequilibrium, Mitochondria, Mice, Inbred C57BL, Mice, Mice, Congenic, Phenotype, Mice, Inbred DBA, Mutation, NADP Transhydrogenases, Animals, Female, Alleles
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).178 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!