Date of Award


Degree Type


Degree Name

Master of Science




Dr. Kathleen Hill


The harlequin (hq)/Big Blue® mouse, a novel model of oxidative stress- induced heart disease with transgene targets for assay of in vivo mutations, was used to assess the effects of elevated reactive oxygen species (ROS) on mutagenesis in the heart. The e ll transgene was used as the mutation target given the detection of a germline mutation in the lacltransgene. Mutations were examined 15 days following a single i.p. injection of the ROS producer, paraquat (10mg/kg) or vehicle control in adult hq/Big Blue® and wild type mice. Despite elevated endogenous superoxide anion levels in heart tissue from hq mice, the frequency and pattern o f mutation in heart tissue ofhq/BigBlue®andwild type mice were similar. The paraquat exposure did not alter the frequency and pattern of mutations. The data initiate the evaluation of hqtBig Blue® mice as a biomonitor for ROS effects and provide improved parameters for experimental design.



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