Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene.
Manganese superoxide dismutase (MnSOD) is the enzyme that converts toxic O(2)(-) to H(2)O(2) in mitochondria. Previous reports showed that a deficiency of MnSOD in mice was neonatal lethal. Therefore, a model mouse was not available for the analysis of the pathological role of O(2)(-) injuries in adult tissues. To explore an adult-type model mouse, we designed tissue-specific MnSOD conditional knockout mice using a Cre-loxp system. First, we crossbred MnSOD flox mice with transgenic mice expressing Cre recombinase under the control of the chicken actin promoter (CAG). We confirmed that CAG MnSOD knockout mice were completely deficient in MnSOD and died as neonates, validating the use of the Cre-loxp system. Next, we generated liver-specific MnSOD-deficient mice by crossbreeding with Alb-Cre transgenic mice. MnSOD activity and protein were both significantly downregulated in the liver of liver-specific MnSOD knockout mice. However, no obvious morphological abnormality was observed in the liver when biochemical alterations such as lipid peroxidation were not detectable, suggesting a redundant or less important physiological role for MnSOD in the liver than previously thought. In the present study, we successfully generated tissue-specific MnSOD conditional knockout mice that would provide a useful tool for the analysis of various age-associated diseases such as diabetes mellitus, Parkinson's disease, stroke, and heart disease, when crossbred with tissue-specific transgenic Cre mice.
Ikegami
Takashi
T
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Suzuki
Yo-ichi
Y
Shimizu
Takahiko
T
Isono
Kyo-ichi
K
Koseki
Haruhiko
H
Shirasawa
Takuji
T
D000199:Actins / Q000235:genetics; D000818:Animals; D002645:Chickens; D004195:Disease Models, Animal; D019426:Integrases / Q000235:genetics; D015227:Lipid Peroxidation; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics
D000199:Actins; D014764:Viral Proteins; D013482:Superoxide Dismutase; C045073:Cre recombinase; D019426:Integrases