Mice that are homozygous for this targeted mutation of Sod3 (superoxide dismutase 3, extracellular) have increased extracellular superoxide radical concentration and exhibit increased sensitivity to experimentally induced hyperoxia, diabetes, inflammation, fibrosis, and hypertension. This mutant mouse strain may be useful in studies of oxidative stress and damage, inflammatory response, hypoxia, ischemia and reperfusion (I/R) injury, and alloxan-induced diabetes.
James D Crapo, Natl Jewish Med & Res CtrRead More +
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size, but reproductive performance is inconsistent for homozygous X homozygous crosses. No gene product (EC-SOD protein) activity is detected by gel-exclusion chromatography analysis of plasma and no protein is detected by Western blot analysis of blood vessels. EC-SOD activity is not detected in brain. When exposed to >99% oxygen conditions, homozygotes have a shorter survival time than wild-type controls and exhibit a more severe lung edema at death. Homozygotes are more sensitive to induced transient focal cerebral ischemia, which results in greater total infarct volume and more severe hemiparesis. Alloxan-induced diabetes causes increased initial hyperglycemia with delayed recovery of glycemic control. Extracellular superoxide radical concentration is doubled and normal age-related loss of endothelial cells is increased in the cornea. Mutant mice are more susceptible to LPS-induced inflammation of the cornea and lung. Homozygotes exhibit increased vascular nitric oxide consumption, higher levels of vascular superoxide anions, weakened nitric oxide mediated endothelium-derived vasodilation (relaxation) in the brain and aorta and are more sensitive to CNS oxygen toxicity. Hippocampal neurogenesis after ionizing irradiation treatment is improved compared to wildtype controls. Homozygotes are more susceptible to bleomycin-induced pulmonary fibrosis, angiotensin II-induced hypertension, and reperfusion injury in skeletal muscle with delayed and incomplete recovery. Levels of the oxidant stress marker, plasma thiobarbituric acid-reactive substances (TBARS), are elevated. Mutant mice exhibit more severe collagen-induced arthritis (on the DBA/1J background). Response to crocidolite-induced asbestosis is enhanced with increased inflammation and total bronchoalveolar lavage fluid protein with more oxidative damage of lung tissue. Myocardial-infarction (MI)-induced heart failure results in increased ventricular hypertrophy and fibrosis. Serum erythropoietin is increased but without a corresponding increase in hematocrit and reticulocyte counts in response to hypoxia. This mutant mouse strain may be useful in studies of oxidative stress and damage, inflammatory response, hypoxia, ischemia and reperfusion (I/R) injury, and alloxan-induced diabetes.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the coding exon. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reported that the resulting chimeric male animals were crossed to C57BL/6 females, and then backcrossed to C57BL/6J (see SNP note below) for 10 generations.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Stefan L Marklund|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||EC-SOD-; ecSOD-|
|Gene Symbol and Name||Sod3, superoxide dismutase 3, extracellular|
|Gene Synonym(s)||AI314465; EC-SOD; ECSODPT; MGC:13799; expressed sequence AI314465|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Sequence encoding the active site of the protein was disrupted by the insertion of a neomycin selection cassette. Superoxide dismutase activity was undetected in plasma obtained from homozygous mutant mice.|
|Mutations Made By|| |
LingYi Chang, Natl Jewish Med & Res Ctr
When maintaining a live colony, these mice can be bred as homozygotes, but reproductive performance can be inconsistent.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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