Manganese Superoxide Dismutase Knockout in Lymphoma

Mice homozygous for the floxed MnSOD allele (i.e. B6.Cg-Sod2^tm1, shorthand MnSOD^L/L) were initially bred to mice expressing Cre-recombinase under the control of the vav promoter (i.e. B6.Cg-Tg-Vav1-iCre^A2Kio/J, shorthand vav-Cre mice, Jackson Laboratories) to create hematopoietic stem cell specific knock-outs of MnSOD [7] (link), [10] (link). These mice were sequentially bred to either an oncogenic model of splenic lymphoma (i.e. B6.Cg-Tg-iMyc^Eμ, shorthand iMyc^+/−) or a conditional tumor suppressor knock-out model of thymic and splenic lymphoma (i.e. FVB.129-Trp53^tm1Brn, shorthand p53^L/L, NCI-Frederick Mouse Repository) [11] (link), [12] (link). In all experiments, littermate controls were used to limit the effects of genetic variation amongst strains. Upon weaning, mice were analyzed by tail DNA to confirm appropriate genotype. Mice were observed until death with no additional challenges. Upon death or illness, all mice were examined by full necropsy and cause of death recorded. Kaplan-Meier with Log-Rank analysis was performed and non-cancer deaths were appropriately censored. Causes of death were compared between groups and analyzed by unpaired two-tail Student's t-test. A p value of less than 0.01 was considered significant. All work was performed under the approval of the Institutional Animal Care and Use Committee at the University of Iowa.