GENETIC-DETERMINANTS OF SUSCEPTIBILITY TO EXCITOTOXIC CELL-DEATH - IMPLICATIONS FOR GENE TARGETING APPROACHES

Recent studies have sought to identify the genes involved in excitotox ic neurodegeneration. Here we report that certain strains of mice, inc luding strains that are used for gene targeting studies, do not exhibi t excitotoxic cell death after kainic acid seizures. Kainic acid produ ced excitotoxic cell death in the CA3 and CA1 subfields of the hippoca mpus in 129/SvEMS and FVB/N mice, in the same pattern as described in rats. C57BL/6 and BALB/c mice exhibited excitotoxic cell death only at very high doses of kainate, and then only in a very restricted area, although they exhibited comparable seizures. Hybrids of 129/SvEMS x C5 7BL/6 mice created using embryonic stem cells from 129/SvEMS mice also did not exhibit excitotoxic cell death. These results demonstrate tha t C57BL/6 and BALB/c strains carry gene(s) that convey protection from glutamate-induced excitotoxicity. This differential susceptibility to excitotoxicity represents a potential complication for gene targeting studies.