October 2014 A model mouse strain for Dravet syndrome


A model mouse strain for Dravet syndrome

B6.129P2-Scn1a<tm1.1Kzy>/KzyRbrc (RBRC06358)


Convulsive seizure in a mouse with an introduced nonsense mutation
in the Scn1a gene.

(Photos courtesy of Kazuhiro Yamakawa, Ph.D.)


Dravet syndrome, or severe myoclonic epilepsy of infancy, is a severe form of epileptic encephalopathy. Patients exhibit recurrent intractable seizures in the first year of life. A major cause of this syndrome is heterozygous mutation of the SCN1A gene that encodes the voltage-gated sodium channel αI subunit Nav1.1, which is required for the proper function of brain cells. A team of researchers led by Kazuhiro Yamakawa generated a knock-in mouse line carrying a premature stop codon (R1407X) in the mouse Scn1a gene [1]. The group demonstrated that Nav1.1 was clustered at the axon initial segments of parvalbumin-positive interneurons in the neocortex and hippocampus. They also showed that Nav1.1 haploinsufficiency causes epileptic seizure, learning/memory impairment, and abnormal social behavior in mice [2-4]. This mouse strain will stimulate further research identifying the mechanisms and pathways involved in Dravet syndrome.


Depositor : Kazuhiro Yamakawa, Ph.D.
Laboratory for Neurogenetics, RIKEN Brain Science Institute
Strain name : B6.129P2-Scn1a<tm1.1Kzy>/KzyRbrc
RBRC No. : RBRC06358
Model to human diseases : Dravet syndrome
OMIM ID: 607208
Epilepsy, generalized, with febrile seizures plus, type 2
OMIM ID: 604403
Febrile seizures, familial, 3A
OMIM ID: 604403
Migraine, familial hemiplegic, 3
OMIM ID: 609634
References : [1] Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, Itohara S, Yanagawa Y, Obata K, Furuichi T, Hensch TK, Yamakawa K. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci.; 27(22):5903-14, 2007.
[2] Cao D, Ohtani H, Ogiwara I, Ohtani S, Takahashi Y, Yamakawa K, Inoue Y. Efficacy of stiripentol in hyperthermia-induced seizures in a mouse model of Dravet syndrome. Epilepsia; 53(7):1140-5, 2012.
[3] Ito S, Ogiwara I, Yamada K, Miyamoto H, Hensch TK, Osawa M, Yamakawa K. Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. Neurobiol Dis.; 49:29-40, 2013.
[4] Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, Yanagawa Y, Tamamaki N, Hensch TK, Itohara S, Yamakawa K. Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome. Hum Mol Genet.; 22(23):4784-804, 2013.


October 2014
Contact: Shinya Ayabe, Ph.D.
Experimental Animal Division, RIKEN BioResource Center
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