title: Identification of QTLs involved in the development of amygdala kindling in the rat.
abstract: Amygdala kindling is useful for modeling human epilepsy development. It has been known that genetic factors are involved in the development of amygdala kindling. The purpose of this study was to identify the loci that are responsible for the development of amygdala kindling. To achieve this, rat strains from a LEXF/FXLE recombinant inbred (RI) strain panel were used. The phenotypes of amygdala kindling-related parameters for seven RI strains and parental LE/Stm and F344/Stm strains were determined. They included the afterdischarge threshold (ADT), the afterdischarge duration (ADD), and the kindling rate, an incidence of development of kindling. Quantitative trait loci (QTL) analysis was performed to identify linkage relationships between these phenotypes and 1,033 SNP markers. Although no significant differences in pre-kindling ADT and ADD were observed, a significant difference in the kindling rate was found for the LEXF/FXLE RI strain. Two QTLs for the amygdala kindling rate (Agkr1 and Agkr2) were identified on rat chromosome 2. These findings clearly prove the existence of genetic influences that are involved in kindling development and suggest that substantial genetic components contribute to the progression of partial seizures into generalized seizures.
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Birger
authors.initials: B
authors.lastname: Voigt
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimaru
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hokao
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Sasa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
mesh_terms: D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics*; D020937:Epilepsy, Partial, Sensory / Q000235:genetics; D006801:Humans; D007696:Kindling, Neurologic / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D020318:Rats, Long-Evans; D012640:Seizures / Q000235:genetics
references.citation: Epilepsy Res. 1999 Jul;35(3):183-95
references.pmid: 10413314
references.citation: Behav Genet. 1991 Mar;21(2):99-116
references.pmid: 2049054
references.citation: Nat Genet. 2008 May;40(5):516-22
references.pmid: 18443588
references.citation: Eur J Neurosci. 2001 Apr;13(8):1501-19
references.pmid: 11328345
references.citation: J Neurochem. 2008 Dec;107(5):1335-46
references.pmid: 18808451
references.citation: Exp Anim. 2009 Jul;58(4):333-41
references.pmid: 19654430
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D658-62
references.pmid: 17151068
references.citation: Nat Genet. 2008 May;40(5):560-6
references.pmid: 18443594
references.citation: Epilepsia. 2005;46 Suppl 5:3-9
references.pmid: 15987246
references.citation: Neurology. 2001 Jan 23;56(2):166-72
references.pmid: 11160950
references.citation: Exp Anim. 2006 Apr;55(2):91-5
references.pmid: 16651691
references.citation: Physiol Genomics. 2008 Feb 19;32(3):335-42
references.pmid: 18042833
references.citation: Exp Neurol. 1998 Dec;154(2):551-9
references.pmid: 9878190
references.citation: Neuron. 2006 Mar 2;49(5):697-706
references.pmid: 16504945
references.citation: Transplantation. 1971 Mar;11(3):325-7
references.pmid: 5558564
references.citation: Mamm Genome. 1997 May;8(5):324-7
references.pmid: 9107675
references.citation: Br J Cancer. 1999 May;80(5-6):855-61
references.pmid: 10360666
references.citation: Exp Neurol. 1969 Nov;25(3):295-330
references.pmid: 4981856
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):269-79
references.pmid: 4110396
references.citation: J Neurosci. 2008 Jun 25;28(26):6583-91
references.pmid: 18579731
references.citation: BMC Genet. 2006 Apr 04;7:19
references.pmid: 16584579
references.citation: Eur J Neurosci. 2004 Jul;20(1):185-94
references.pmid: 15245491
references.citation: J Chem Neuroanat. 2005 Jul;30(1):1-16
references.pmid: 15921884