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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1820.)
© 2003 American Heart Association, Inc.

Vascular Biology

Extracellular Superoxide Dismutase Polymorphism in Mice

Anson Pierce; Jason Whitlark; Ladislav Dory

From the Department of Molecular Biology & Immunology, University of North Texas Health Science Center at Fort Worth, Tex.

Correspondence to Ladislav Dory, UNT Health Science Center at Fort Worth, Department of Molecular Biology & Immunology, 3500 Camp Bowie Blvd, Fort Worth, TX. E-mail ldory{at}hsc.unt.edu

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 C57Bl/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.

Key Words: extracellular superoxide dismutase • apolipoprotein E^-/-/LDLR^-/- mice • atherosclerosis • antioxidant response • oxidation