TY - JOUR
T1 - Extracellular superoxide dismutase polymorphism in mice
AU - Pierce, Anson
AU - Whitlark, Jason
AU - Dory, Ladislav
PY - 2003/10
Y1 - 2003/10
N2 - 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.
AB - 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.
KW - Antioxidant response
KW - Apolipoprotein E/LDLR mice
KW - Atherosclerosis
KW - Extracellular superoxide dismutase
KW - Oxidation
UR - http://www.scopus.com/inward/record.url?scp=0141954207&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000089011.51491.A6
DO - 10.1161/01.ATV.0000089011.51491.A6
M3 - Article
C2 - 12893682
AN - SCOPUS:0141954207
SN - 1079-5642
VL - 23
SP - 1820
EP - 1825
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 10
ER -