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Melior Discovery neurology

Audiogenic Seizure in Fmr1 Knockout Mice
Fragile X patients have a mutation in the Fmr1 gene in which the product of the gene, (FMRP; fragile X mental retardation protein), is not expressed.  FMRP is an RNA binding protein that plays a pivitol role in synaptic functioning by translational regulation of dendritic mRNAs.  Fmr1 KO mice are a clinically translatable model of fragile X syndrome (FXS) and they recapitulate many of the phenotypic behavioral characteristics of the fragile X syndrome in humans.  For example, Fmr1 KO mice have an increased susceptibility to audiogenic seizures (AGS), or seizure precipitated by a loud noise.

Mice are exposed to two presentations of a loud alarm and the seizure activity is observed and scored according to a four point severity score. Animals are considered to have had a seizure if the seizure severity score is two or above.
                     Audiogenic Seizure in Fmr1 KO mice and r-baclofen

Audiogenic seizure. Fmr1 knockout (KO) mice are significantly more susceptible to AGS than wild-type (WT) control mice (A).  R-baclofen, the more active enantiomer of the GABA B receptor against baclofen, dose-dependently reduces AGS in Fmr1 KO mice.  Data are mean ± SEM; **p<0.01, ***p<0.001 compared to KO vehicle. 

If you are interested in learning more about the Audiogenic Seizure model, please contact models@meliordiscovery.com to start the conversation.