Increased expression of 3-hydroxyanthranilate 3,4-dioxygenase gene in brain of epilepsy-prone El mice

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The El mouse is an established animal model for human epilepsy. We previously reported that the level of quinolinic acid (QUIN), an excitotoxin, was high in the brain of epilepsy-prone El mice and that the increased production of QUIN was secondary to an increased activity of 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO, EC 1.13.11. 6) in the brains of these mice. In this study, we cloned and sequenced the cDNA for 3-HAO and showed that its expression in the brain of El mice was higher than that of control ddY mice. These results suggest that a genetic defect leading to derepression of the 3-HAO gene expression in the brain may be involved in the pathogenesis for the epileptic diseases of El mice.

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