title: Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment.
abstract: Dravet syndrome is an intractable epileptic encephalopathy characterized by early onset epileptic seizures followed by cognitive decline, hyperactivity, autistic behaviors and ataxia. Most Dravet syndrome patients possess heterozygous mutations of SCN1A gene encoding voltage-gated sodium channel αI subunit (Nav1.1). We have previously reported that mice heterozygous for a nonsense mutation in Scn1a developed early onset epileptic seizures. However, the learning ability and sociability of the mice remained to be investigated. In the present study, we subjected heterozygous Scn1a mice to a comprehensive behavioral test battery. We found that while heterozygous Scn1a mice had lowered spontaneous motor activity in home cage, they were hyperactive in novel environments. Moreover, the mice had low sociability and poor spatial learning ability that correspond to the autistic behaviors and cognitive decline seen in Dravet syndrome patients. These results suggest that Nav1.1 haploinsufficiency intrinsically contributes to not only epileptic seizures but also lowered sociability and learning impairment in heterozygous Scn1a mutant mice, as it should also be the case in patients with Dravet syndrome.
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Department of Pediatrics, Graduate School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ito
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ogiwara
authors.affiliation: Laboratory for Support Unit for Animal Resources Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; PRESTO, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Northwest Building, 52 Oxford Street, NW 347.10, Cambridge, MA 02138, USA; Department of Neurology, FM Kirby Neurobiology Center, Children's Hospital Boston, Harvard Medical School, 320 Longwood Ave, CLS 13036, Boston, MA 02115, USA.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: yamakawa@brain.riken.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000523:psychology*; D006120:Grooming / Q000502:physiology; D057895:Haploinsufficiency; D007859:Learning Disabilities / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000172:deficiency* / Q000235:genetics; D012193:Reversal Learning / Q000502:physiology; D045442:Rotarod Performance Test; D012903:Smell / Q000502:physiology; D012919:Social Behavior
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568249:Scn1a protein, mouse