Epilepsy – Audiogenic seizures in the FMR1 Fragile X model (AUX)
Fragile X Syndrome, an X-linked disorder, is the most common form of inherited mental retardation worldwide. A Fragile X mouse model is created by mating homozygous females and wild type males (FVBN129P2) with a mutation in the X-linked Fmr1 gene. These mice have a substantial sensitivity to audiogenic seizures (AUX), and signaling through metabotropic glutamate receptors may also be altered. FMR1 mutant mice at 21 days of age are exposed to a high intensity tone (125 dB) in a sound-attenuating chamber. Audiogenic seizures generally begin with a period of wild running and jumping, leading to seizures (clonic, clonic/tonic, tonic), and often respiratory arrest and death. The mGluR5 antagonists MPEP and MTEP significantly increase the duration to seizure onset and respiratory distress, and subsequently decrease mortality.
MPEP (10 and 30mpk) and MTEP significantly increase the duration to seizure onset, with complete absence of seizures for MPEP 30mpk.
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