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

doi:10.1007/s10519-017-9870-2

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 journal › Article

2 Citations (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 G_αi-interacting protein involved in GABA_B receptor signaling pathway. Based on these findings, we conclude that Cckbr, St5, and Phf24 are strong candidate genes for GTCS in NER.

Original language	English
Pages (from-to)	609-619
Number of pages	11
Journal	Behavior Genetics
Volume	47
Issue number	6
DOIs	https://doi.org/10.1007/s10519-017-9870-2
Publication status	Published - Nov 1 2017

All Science Journal Classification (ASJC) codes

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

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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, 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 journal › Article

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, 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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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.",

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AU - Nakamura, Tadashi

AU - Wakamatsu, Kaori

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AU - Suyama, Mikita

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AU - Tanaka, Miyuu

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AU - Ohno, Yukihiro

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AU - Serikawa, Tadao

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