Extracellular superoxide dismutase polymorphism in mice

Anson Pierce, Jason Whitlark, Ladislav Dory

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objective - In this study, we describe a previously unrecognized murine extracellular superoxide dismutase (ecSOD) allele and examine its distribution among various strains and its effect on the ecSOD phenotype. Methods and Results - Polymerase chain reaction analysis of genomic and cDNA from apolipoprotein E/LDLR-/- mice indicates the presence of 2 distinct transcripts for this enzyme independent of the extent of atherosclerosis or age. Sequencing and genotyping analyses reveal the presence of 2 alleles for ecSOD. One is a short variant with a 10-base pair deletion in the 3′UTR, accompanied by a single nucleotide substitution (position 61) found in the 129P3/J strain of mice. By contrast, all other strains examined carry the long form. Both free and heparin-releasable ecSOD activities in the 129P3/J strain are more than 3-fold higher than those in the C57B1/6 mice. Corresponding differences in plasma enzyme mass are observed by immunoblotting. A clear allele dose effect can be observed in F2 hybrids of these 2 strains; free and total ecSOD activities in mice homozygous for the short allele are twice those of mice homozygous for the long allele, with the heterozygote values in between. Conclusions - These data clearly demonstrate the allele-specific effects on the ecSOD phenotype independent of other strain-specific factors and underline the need for backcrossing of genetically modified mice.

Original languageEnglish (US)
Pages (from-to)1820-1825
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2003

Keywords

  • Antioxidant response
  • Apolipoprotein E/LDLR mice
  • Atherosclerosis
  • Extracellular superoxide dismutase
  • Oxidation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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