title: Development and Validation of a New Mouse Model to Investigate the Role of SV2A in Epilepsy.
abstract: SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless, Levetiracetam, a very effective anti-epileptic drug, has been recently demonstrated to bind to SV2A. At present, our understanding of the normal function of SV2A and its possible involvement in diseases like epilepsy is limited. With this study, we sought to develop a relevant model enabling analysis of SV2A's role in the occurrence or progression of epilepsy. For this purpose, we generated a floxed SV2A mouse model with conditional alleles carrying LoxP sites around exon 3 by means of a gene-targeting strategy. The SV2A lox/lox mouse line is indistinguishable from wild-type mice. When the recombination was observed in all cells, a model of mice with both SV2A alleles floxed around exon 3 recapitulated the phenotype of SV2A KO mice, including seizures. However, the specific invalidation of SV2A in the CA3 hippocampal region was not followed by epileptic seizures or decrease in the epileptic threshold on pentylenetetrazol (PTZ) test. These results demonstrate that the floxed SV2A mouse line has been successfully established. This transgenic mouse model will be useful for investigating SV2A functions related to cell types and developmental stages.
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Menten-Dedoyart
authors.affiliation: Cyclotron Research Center, University of Liège, Liège, Belgium.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Serrano Navacerrada
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Odile
authors.initials: O
authors.lastname: Bartholome
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Judit
authors.initials: J
authors.lastname: Sánchez Gil
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Neirinckx
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wislet
authors.affiliation: Cyclotron Research Center, University of Liège, Liège, Belgium.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Becker
authors.affiliation: Cyclotron Research Center, University of Liège, Liège, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Plenevaux
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Van den Ackerveken
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.|Neurology Department, CHU, Academic Hospital, University of Liège, Liège, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rogister
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D017930:Genes, Reporter; D056426:Genetic Loci; D005822:Genetic Vectors / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D059765:Homologous Recombination; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489614:Sv2a protein, mouse