Neuropathologic findings associated with seizures in FVB mice

The FVB mouse is used extensively in transgenic research because of its defined inbred background, superior reproductive performance, and prominent pronuclei, which facilitate microinjection of genomic material. Seizures associated with a known mutation and seizure-susceptible inbred strains are well documented in mice; however, to the authors' knowledge, seizures in the FVB strain have not been evaluated. Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice generated, using eight unrelated transgenic constructs (n = 63), were submitted for pathologic examination. Most cases were detected during routine observations in animal rooms; however, seizure induction by tail tattooing, fur clipping, and fire alarms has been observed. The majority of mice were female (62 of 68), with mean age of 5.8 months (range, 2 to 16 months). Observations made during seizure presentation in 12 of 68 mice included facial grimace, chewing automatism, ptyalism with matting of the fur of the ventral aspect of the neck and/or forelimbs, and clonic convulsions that frequently progressed to tonic convulsions and death. Four mice were dead at presentation, with matting of the fur of the neck and forelimbs. The remainder of the mice had nonspecific signs of disease, such as lethargy, moribundity, or matting of the fur. Vendor and in-house animal health surveillance reports indicated that mice were seronegative to all murine pathogens. Results of gross pathologic examination were unremarkable. Microscopic findings were limited to the brain and liver. In all mice, neuronal necrosis was present in the cerebral cortex, hippocampus, and thalamus. Concurrent astrocyte hypertrophy, as evidenced by an increase in glial fibrillary acidic protein staining, was detected. Acute coagulative necrosis of centrilobular hepatocytes was present in the liver of some cases (19 of 68). Infective agents were not detected in selected brain specimens submitted for electron microscopy or in brain and liver specimens evaluated by use of special stains. Cytopathologic effect was not observed in 3T3, Vero, and BHK-21 cell lines inoculated with brain and liver specimens. The ischemic neuronal necrosis observed in these mice is consistent with lesions associated with status epilepticus in humans. The hepatocellular changes are interpreted to be agonal and associated with terminal hypoxia in seizuring animals. These results provide evidence of a previously unrecognized, often lethal epileptic syndrome in FVB mice that may have a major impact on transgenic research and other disciplines using this mouse strain.