Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat

Takashi Kuramoto, Birger Voigt, Satoshi Nakanishi, Kazuhiro Kitada, Tadashi Nakamura, Kaori Wakamatsu, Minako Yoshihara, Mikita Suyama, Risa Uemura, Miyuu Tanaka, Mitsuru Kuwamura, Saki Shimizu, Yukihiro Ohno, Masashi Sasa, Tadao Serikawa

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    The Noda epileptic rat (NER) exhibits generalized tonic–clonic seizures (GTCS). A genetic linkage analysis identified two GTCS-associated loci, Ner1 on Chr 1 and Ner3 on Chr 5. The wild-type Ner1 and Ner3 alleles suppressed GTCS when combined in double-locus congenic lines, but not when present in single-locus congenic lines. Global expression analysis revealed that cholecystokinin B receptor (Cckbr) and suppressor of tumorigenicity 5 (St5), which map within Ner1, and PHD finger protein 24 (Phf24), which maps within Ner3, were significantly downregulated in NER. De novo BAC sequencing detected an insertion of an endogenous retrovirus sequence in intron 2 of the Phf24 gene in the NER genome, and PHF24 protein was almost absent in the NER brain. Phf24 encodes a Gαi-interacting protein involved in GABAB receptor signaling pathway. Based on these findings, we conclude that Cckbr, St5, and Phf24 are strong candidate genes for GTCS in NER.

    Original languageEnglish
    Pages (from-to)609-619
    Number of pages11
    JournalBehavior Genetics
    Volume47
    Issue number6
    DOIs
    Publication statusPublished - Nov 1 2017

    Fingerprint

    Genetic Association Studies
    seizures
    Seizures
    Fingers
    protein
    gene
    rats
    Cholecystokinin B Receptor
    Proteins
    genes
    proteins
    loci
    Retroviridae
    Endogenous Retroviruses
    Genetic Linkage
    Introns
    linkage (genetics)
    seizure
    brain
    introns

    All Science Journal Classification (ASJC) codes

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Genetics(clinical)

    Cite this

    Kuramoto, T., Voigt, B., Nakanishi, S., Kitada, K., Nakamura, T., Wakamatsu, K., ... Serikawa, T. (2017). Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat. Behavior Genetics, 47(6), 609-619. https://doi.org/10.1007/s10519-017-9870-2

    Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat. / Kuramoto, Takashi; Voigt, Birger; Nakanishi, Satoshi; Kitada, Kazuhiro; Nakamura, Tadashi; Wakamatsu, Kaori; Yoshihara, Minako; Suyama, Mikita; Uemura, Risa; Tanaka, Miyuu; Kuwamura, Mitsuru; Shimizu, Saki; Ohno, Yukihiro; Sasa, Masashi; Serikawa, Tadao.

    In: Behavior Genetics, Vol. 47, No. 6, 01.11.2017, p. 609-619.

    Research output: Contribution to journalArticle

    Kuramoto, T, Voigt, B, Nakanishi, S, Kitada, K, Nakamura, T, Wakamatsu, K, Yoshihara, M, Suyama, M, Uemura, R, Tanaka, M, Kuwamura, M, Shimizu, S, Ohno, Y, Sasa, M & Serikawa, T 2017, 'Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat', Behavior Genetics, vol. 47, no. 6, pp. 609-619. https://doi.org/10.1007/s10519-017-9870-2
    Kuramoto T, Voigt B, Nakanishi S, Kitada K, Nakamura T, Wakamatsu K et al. Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat. Behavior Genetics. 2017 Nov 1;47(6):609-619. https://doi.org/10.1007/s10519-017-9870-2
    Kuramoto, Takashi ; Voigt, Birger ; Nakanishi, Satoshi ; Kitada, Kazuhiro ; Nakamura, Tadashi ; Wakamatsu, Kaori ; Yoshihara, Minako ; Suyama, Mikita ; Uemura, Risa ; Tanaka, Miyuu ; Kuwamura, Mitsuru ; Shimizu, Saki ; Ohno, Yukihiro ; Sasa, Masashi ; Serikawa, Tadao. / Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat. In: Behavior Genetics. 2017 ; Vol. 47, No. 6. pp. 609-619.
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