title: Evaluation of seizure foci and genes in the Lgi1(L385R/+) mutant rat.
abstract: Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically relevant features of Lgi1 heterozygous mutant rats (Lgi1(L385R/+)) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1(L385R/+) and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1(L385R/+) rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1(L385R/+) rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1(L385R/+) rats are useful as an animal model of human ADLTE.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fumoto
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address: tmashimo@anim.med.kyoto-u.ac.jp.
authors.forename: Tomoji
authors.initials: T
authors.lastname: Mashimo
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masui
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Mizuguchi
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Minamimoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ohno
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D020195:Epilepsy, Reflex / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C492120:Lgi1 protein, mouse; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos
keywords: ADLTE; EEG; Fos; LGI1; Microarray; Rats