Audiogenic Seizure in Fmr1 Knockout Mice

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Fragile X patients have a mutation in the Fmr1 gene in which the gene, (FMRP; fragile X mental retardation protein), is not expressed. FMRP is an RNA binding protein that plays a pivotal role in synaptic functioning by translational regulation of dendritic mRNAs.

Fmr1 knockout (KO) mice have an increased susceptibility to audiogenic seizures (Thomas et al., 2011; Veeraragavan et al., 2011; Osterweil et al., 2010). Moreover, Fmr1 KO mice are reported to exhibit deficits in learning and memory tests such as fear conditioning (Zhao et al., 2005; Hayashi et al., 2007; Guo et al., 2012; Gu et al., 2002). Overall, this animal model is considered to be a clinically translatable model of fragile X syndrome.

After evaluating locomotor activity, mice are placed into Audiogenic Seizure test chambers with attached alarms. After acclimating, animal behavior is recorded for a 2 minute alarm challenge, a 1 minute resting period and an additional 2 minute challenge.

Audiogenic seizure score in Fmr1 KO mice is reduced with R-baclofen treatment.

In the figure above, mice were scored based on their behavior according to a four point severity score.  Animals are considered to have a seizure if the severity score is two or above.  R-baclofen significantly reduces the seizure score at 3mg/kg dose and eliminates seizure at 6mg/kg dose. Data are mean ± SEM; **p<0.01, ***p<0.001 compared to vehicle; #p<0.05 R-baclofen dose response (N=15).


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