Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome.
OBJECTIVE
To evaluate their susceptibility to audiogenic seizures, five groups of knockout mice with various forms of fragile X genetic involvement [hemizygous males (n = 46), and homozygous (n = 38) and heterozygous females (n = 45), and their normal male (n = 45) and female (n = 52) littermates] were studied.


METHODS
All mouse groups were tested at ages 17, 22, 35, and 45 days. Audiogenic seizure susceptibility was scored, and the analysis of variance was used for the evaluation of the effects of age and genetic condition on seizure 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. Hemizygous males showed higher SSSs with increasing age, from 17 to 45 days; homozygous females showed a peak at age 22 days, followed by a decrease; finally, heterozygous females had their highest SSSs at age 17 days.


CONCLUSIONS
This study demonstrates that an increased susceptibility to audiogenic seizures is present in fragile X knockout mice at all the ages tested. These results support the validity of this animal model also for epilepsy and seizures in the human fragile X syndrome.
Musumeci
S A
SA
Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging, Troina, Italy. samusumeci@oasi.en.it
Bosco
P
P
Calabrese
G
G
Bakker
C
C
De Sarro
G B
GB
Elia
M
M
Ferri
R
R
Oostra
B A
BA
D000161:Acoustic Stimulation / Q000009:adverse effects*; D000375:Aging / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D020195:Epilepsy, Reflex / Q000209:etiology* / Q000235:genetics; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic