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 language | English |
|---|---|
| Pages (from-to) | 609-619 |
| Number of pages | 11 |
| Journal | Behavior Genetics |
| Volume | 47 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Nov 1 2017 |
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All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Genetics(clinical)
Cite this
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
}
TY - JOUR
T1 - Identification of Candidate Genes for Generalized Tonic–Clonic Seizures in Noda Epileptic Rat
AU - Kuramoto, Takashi
AU - Voigt, Birger
AU - Nakanishi, Satoshi
AU - Kitada, Kazuhiro
AU - Nakamura, Tadashi
AU - Wakamatsu, Kaori
AU - Yoshihara, Minako
AU - Suyama, Mikita
AU - Uemura, Risa
AU - Tanaka, Miyuu
AU - Kuwamura, Mitsuru
AU - Shimizu, Saki
AU - Ohno, Yukihiro
AU - Sasa, Masashi
AU - Serikawa, Tadao
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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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U2 - 10.1007/s10519-017-9870-2
DO - 10.1007/s10519-017-9870-2
M3 - Article
VL - 47
SP - 609
EP - 619
JO - Behavior Genetics
JF - Behavior Genetics
SN - 0001-8244
IS - 6
ER -