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

被引：13

作者：

Kuramoto, Takashi ^{[1
]}

Voigt, Birger ^{[1
]}

Nakanishi, Satoshi ^{[1
]}

Kitada, Kazuhiro ^{[2
]}

Nakamura, Tadashi ^{[3
]}

Wakamatsu, Kaori ^{[3
]}

Yoshihara, Minako ^{[4
]}

Suyama, Mikita ^{[4
]}

Uemura, Risa ^{[5
]}

Tanaka, Miyuu ^{[1
,5
]}

Kuwamura, Mitsuru ^{[5
]}

Shimizu, Saki ^{[6
]}

Ohno, Yukihiro ^{[6
]}

Sasa, Masashi ^{[7
]}

Serikawa, Tadao ^{[1
,6
]}

机构：

[1] Kyoto Univ, Inst Lab Anim, Grad Sch Med, Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan

[2] Hokkaido Univ, Grad Sch Sci, Div Biosci, Sapporo, Hokkaido 0600810, Japan

[3] Gunma Univ, Grad Sch Sci & Technol, Div Mol Sci, 1-5-1 Tenjin, Kiryu, Gunma 3768515, Japan

[4] Kyushu Univ, Med Inst Bioregulat, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan

[5] Osaka Prefecture Univ, Lab Vet Pathol, Izumisano, Osaka 5988531, Japan

[6] Osaka Univ Pharmaceut Sci, Pharmacol Lab, Takatsuki, Osaka 5691094, Japan

[7] Nagisa Clin, Hirakata, Osaka 5731183, Japan

来源：

BEHAVIOR GENETICS | 2017年 / 47卷 / 06期

关键词：

Cckbr; Generalized tonic-clonic seizures; Noda epileptic rat; Phf24; St5; TEMPORAL-LOBE EPILEPSY; RECEPTOR; BRAIN; NER; INVOLVEMENT; EXPRESSION; RELEASE; NEURONS; STRAIN; TREMOR;

D O I：

10.1007/s10519-017-9870-2

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

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(alpha i)-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.

引用

页码：609 / 619

页数：11

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