Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome

Purpose: To evaluate their susceptibility to audiogenic seizures, five grou ps Of knockout mice with various forms of fragile X genetic involvement [he mizygous males (n = 46), and homozygous (n = 38) and heterozygous females ( n = 45) and their normal male (n = 45) and female (n = 52) littermates] wer e studied. Methods; All mouse groups were tested at ages 17, 22, 35, and 45 days. Audi ogenic seizure susceptibility was scored, and the analysis of variance was used for the evaluation of the effects of age and genetic condition on seiz ure severity score (SSS). Results: All groups of knockout fragile X mice exhibited SSSs significantly higher than those observed in their wild-type littermates; among knockout mice, hemizygous males and homozygous females showed the highest SSSs. Hemi zygous males showed higher SSSs with increasing age, from 17 to 45 days; ho mozygous females showed a peak at age 22 days, followed by a decrease; fina lly, heterozygous females had their highest SSSs at age 17 days. Conclusions: This study demonstrates that an increased sus ceptibility to a udiogenic seizures is present in fragile X knockout mice at all the ages te sted. These results support the validity of this animal model also for epil epsy and seizures in the human fragile X syndrome.