RRC ID 49300
著者 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.
タイトル Identification of Candidate Genes for Generalized Tonic-Clonic Seizures in Noda Epileptic Rat.
ジャーナル Behav. Genet.
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.
巻・号 47(6)
ページ 609-619
公開日 2017-9-25
DOI 10.1007/s10519-017-9870-2
PII 10.1007/s10519-017-9870-2
PMID 28936718
MeSH Animals Chromosomes, Mammalian / genetics DNA-Binding Proteins / genetics Disease Models, Animal Electroencephalography / methods Electroencephalography / veterinary Epilepsy / genetics Epilepsy, Tonic-Clonic / genetics* Genetic Linkage / genetics Genetic Loci / genetics PHD Zinc Fingers / genetics Rats Rats, Wistar / genetics Receptor, Cholecystokinin B / genetics* Receptor, Cholecystokinin B / physiology Seizures / genetics Tumor Suppressor Proteins / genetics*
IF 2.385
ラット NER/Kyo (strainID=26)