Publication Details

Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase.

Authors:Huang TT, Naeemuddin M, Elchuri S, Yamaguchi M, Kozy HM, Carlson EJ, Epstein CJ
Title:Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase.
Journal:Human molecular genetics Apr 2006 , Vol 15 , pp. 1187-94
Abstract: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.   PUBMED: 16497723
Ontological Annotations:
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D005978: Glutathione (Publication, NCBO Annotator)
  • D012038: Regeneration (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • GO:0005739: mitochondrion (Publication, NCBO Annotator)
  • D013534: Survival (Publication, NCBO Annotator)
  • D008565: Membrane Proteins (Publication, NCBO Annotator)
  • D009249: NADP (Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • GO:0016020: membrane (Publication, NCBO Annotator)
  • D013995: Time (Publication, NCBO Annotator)
  • D008566: Membranes (Publication, NCBO Annotator)
  • D002882: Chromosomes, Human, Pair 13 (Publication, NCBO Annotator)
  • D013482: Superoxide Dismutase (Publication, NCBO Annotator)
  • GO:0005743: mitochondrial inner membrane (Publication, NCBO Annotator)
  • D005191: Family Characteristics (Publication, NCBO Annotator)
  • D012380: Role (Publication, NCBO Annotator)
  • GO:0031099: regeneration (Publication, NCBO Annotator)
  • D008928: Mitochondria (Publication, NCBO Annotator)
  • D009250: NADP Transhydrogenase (Publication, NCBO Annotator)
  • D009536: Niacinamide (Publication, NCBO Annotator)
  • D011522: Protons (Publication, NCBO Annotator)
  • GO:0015992: proton transport (Publication, NCBO Annotator)
  • GO:0006810: transport (Publication, NCBO Annotator)
  • D008136: Longevity (Publication, NCBO Annotator)
  • D020297: Mice, Congenic (Publication, NCBO Annotator)
  • D013879: Thioredoxins (Publication, NCBO Annotator)
  • D013481: Superoxides (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier II Mouse 59 Genes GS129189: survival time modifier of Sod2 (Svtms Published QTL Chr 13)