Genetic modifier of mitochondrial superoxide dismutase-deficient mice delays heart failure and prolongs survival
Copyright policy )Genetic modifier of mitochondrial superoxide dismutase-deficient mice delays heart failure and prolongs survival
Mn superoxide dismutase (MnSOD)-deficient mice (Sod2-/-) suffer from mitochondrial damage and have various survival times and phenotypic presentations that are dependent on the genetic background of the mutant mice. The mitochondrial NADPH transhydrogenase (NNT) was identified as a putative genetic modifier based on a genome-wide quantitative trait association study on the molecular defect of the protein in more severely affected Sod2-/- mice and on the biological function of NNT. Hence, Sod2-/- mice on the C57BL/6J (B6J) background have the shortest survival time, and the mice are homozygous for the truncated Nnt allele (Nnt ( T )). On the other hand, genetic backgrounds that support longer survival of Sod2-/- mice all have at least one normal copy of Nnt (Nnt ( W )). To confirm the role of NNT in the phenotypic modification of Sod2-/- mice, we introduced a normal copy of Nnt allele from a C57BL/6 substrain into B6J-Sod2-/- mice and analyzed survival time, cardiac functions, and histopathology of the heart. The study results show that the presence of a normal Nnt allele preserves cardiac function, delays the onset of heart failure, and extends the survival of B6J-Sod2-/- mice to the end of gestation. Postnatal survival, however, is not supported. Consequently, the majority of B6J-Sod2-/- mice died within a few hours after birth and only a few survived for 5-6 days. The study results suggest that NNT is important for normal development and function of fetal hearts and that there may be other genetic modifier(s) important for postnatal survival of Sod2-/- mice.
- Stanford University United States
- University of California, San Francisco United States
- Catholic University of Daegu Korea (Republic of)
- VA Palo Alto Health Care System United States
Heart Failure, Male, Mice, Knockout, Superoxide Dismutase, Homozygote, Gene Expression Regulation, Developmental, NADP Transhydrogenase, AB-Specific, Mice, Inbred C57BL, Mitochondrial Proteins, Mice, Phenotype, Risk Factors, NADP Transhydrogenases, Animals, Female, Alleles
Heart Failure, Male, Mice, Knockout, Superoxide Dismutase, Homozygote, Gene Expression Regulation, Developmental, NADP Transhydrogenase, AB-Specific, Mice, Inbred C57BL, Mitochondrial Proteins, Mice, Phenotype, Risk Factors, 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).34 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 10% 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!