title: Audiogenic seizure susceptibility is reduced in fragile X knockout mice after introduction of FMR1 transgenes.
abstract: The Fmr1 knockout (KO) mouse is characterized by an increased audiogenic seizure (AGS) susceptibility and is considered a good animal model for epilepsy and seizures in the human fragile-X (FRAX) syndrome. Here, we tested the hypothesis that the reintroduction of the FMR1 gene is able to revert the AGS susceptibility characterizing Fmr1 KO mice. To this aim, two groups of Fmr1 KO transgenic mice, which have additional copies of the human FMR1 gene (YAC) or FMR1 cDNA (G6) were used. AGS susceptibility of these mice was examined and compared to that of Fmr1 KO, wild type, and wild-type animals in whom the FMR1gene was also introduced (over-expressed). Mice were tested at different ages because AGS susceptibility is age dependent. The intensity of response was scored and the results were analyzed by means of 2-way analysis of variance to evaluate the effects of age and genetic condition. We found that AGS susceptibility rescue is complete in the G6 mice and partial in YAC mice. Our data indicate that the introduction of the human FMR1 gene in Fmr1 KO mice is able to revert the Fmr1 KO epileptic phenotype.
authors.affiliation: Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy. samusumeci@oasi.en.it
authors.forename: Sebastiano A
authors.initials: SA
authors.lastname: Musumeci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calabrese
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Bonaccorso
authors.forename: Simona
authors.initials: S
authors.lastname: D'Antoni
authors.forename: Judith R
authors.initials: JR
authors.lastname: Brouwer
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Bakker
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Catania
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020195:Epilepsy, Reflex / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D014162:Transfection; D019076:Transgenes / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse