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Amygdara kindling susceptibility loci identified with rat LEXF/FXLE recombinant inbred strains

Research Project

Project/Area Number 18300141
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionKyoto University

Principal Investigator

KURAMOTO Takashi  Kyoto University, 大学院・医学研究科, 准教授 (20311409)

Co-Investigator(Kenkyū-buntansha) SERIKAWA Tadao  京都大学, 医学研究科, 教授 (30025655)
HOKAO Ryoji  動物繁殖研究所, 理事長 (80156992)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsラット / リコンビナント近交系 / 疾患モデル / てんかん / QTL / キンドリング / リコンビナント系統
Research Abstract

実験動物の脳の特定部位を後発射を引き起こすような電流値で毎日刺激すると、顔面けいれん、咀嚼などの行動上のけいれん発作が現れ、最終的に全般発作となる。この現象は、キンドリングと呼ばれ、ヒトてんかんにおける、てんかん原性の獲得から発作の進展という過程を理解する上で有用な実験モデルとされている。本研究では、ラットLEXF/FXLEリコンビナント近交系(RI系統)を用いてキンドリング感受性座位の同定を目的とした。RI系統7系統と親系統(LE/Stm, F344/Stm)に対してキンドリングを誘発し、発作閾値、各刺激における後発射持続時間、キンドリング獲得までの刺激回数 (kindling rate) からなる表現型値を決定した。その結果、発作閾値、各刺激における後発射持続時間では系統差がなかったが、kindling rateには系統差があった。一方、1,033個のSNPマーカーからなる遺伝型を決定した。連鎖解析によって、kindling rateと相関する染色体領域を第2染色体に見出し、Amygdala kindling susceptibility 1 (Aks1)とAks2と名付けた。Aks1, Aks2はキンドリングの進展に関与する遺伝子座であり、ヒトてんかんにおける重大な関心事であるてんかんの全般化に関与する遺伝的要因を含むと考えられる。本研究は、キンドリング発症に係わる遺伝子座が特定し、発作の全般化に関して遺伝的要因が存在することを明らかにした。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (50 results)

All 2009 2008 2007 2006

All Journal Article (32 results) (of which Peer Reviewed: 9 results) Presentation (18 results)

  • [Journal Article] An informative set of SSLP markers and genomic profiles in the rat MHC, the RTl complex2009

    • Author(s)
      Takagi Y, Kuraioto T, et al.
    • Journal Title

      Immunogenetics 61

      Pages: 189-197

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the Kyoto circling (KCI) rat carrying a spontaneous nonsense mutation in the protocadherin 15 (Pcdh15) gene.2009

    • Author(s)
      Naoi K, Kuramoto T, et al.
    • Journal Title

      Exp. Anim. 58

      Pages: 1-10

    • NAID

      130000419478

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic dissection of the LEXF/FXLE recombinant inbred strains2008

    • Author(s)
      Kuramoto T, Voigt B, Mashimo T, Sasaki Y, Hokao R, Serikawa T
    • Journal Title

      Physiol Res 57

    • Related Report
      2008 Final Research Report
  • [Journal Article] The STAR Consortium*, SNP and haplotype mapping for genetic analysis in the rat2008

    • Author(s)
      Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D, Chen Y, Cuppen E, Demonchy S, Dopazo J, Flicek P, Foglio M, Fujiyama A, Gut IG, Gauguier D, Guigo R, Guryev V, Heinig M, Hummel O, Jahn N, Klages S, Kren V, Kube M, Kuhl H, Kuramoto T, Kuroki Y, Lechner D, Lee YA, Lopez-Bigas N, Lathrop GM, Mashimo T, Medina I, Mott R, Patone G, Perrier-Cornet JA, Platzer M, Pravenec M, Reinhardt R, Sakaki Y, Schilhabel M, Schulz H, Serikawa T, Shikhagaie M, Tatsumoto S, Taudien S, Toyoda A, Voigt B, Zelenika D, Zimdahl H, Hubner N
    • Journal Title

      Nat Genet 40(5)

      Pages: 560-566

    • Related Report
      2008 Final Research Report
  • [Journal Article] Progress and prospects in rat genetics : a community view2008

    • Author(s)
      Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, Gauguier D, Geurts AM, Gould M, Harris PC, Holmdahl R, Hubner N, Izsvak Z, Jacob HJ, Kuramoto T, Kwitek AE, Marrone A, Mashimo T, Moreno C, Mullins J, Mullins L, Olsson T, Pravenec M, Riley L, Saar K, Serikawa T, Shull JD, Szpirer C, Twigger SN, Voigt B, Worley K
    • Journal Title

      Nat Genet 40(5)

      Pages: 516-522

    • Related Report
      2008 Final Research Report
  • [Journal Article] An ENU-induced mutant archive for gene targeting in rats2008

    • Author(s)
      Mashimo T, Yanagihara K, Tokuda S, Voigt B, Takizawa A, Nakajima R, Kato M, Hirabayashi M, Kuramoto T, Serikawa T
    • Journal Title

      Nat Genet 40(5)

      Pages: 514-515

    • Related Report
      2008 Final Research Report
  • [Journal Article] N-Acetyl-l-aspartate activates hippocampal CA3 neurons in rodent slice preparations2008

    • Author(s)
      Hanaya R, Kiura Y, Kurisu K, Sakai N, Serikawa T, Sasa M
    • Journal Title

      Brain Res Bull 75(5)

      Pages: 663-667

    • Related Report
      2008 Final Research Report
  • [Journal Article] Pancreatic metaplasia in the gastro-achlorhydria in WTC-dfk rat, a potassium channel Kcnq1 mutant2008

    • Author(s)
      Kuwamura M, Okajima R, Yamate J, Kotani T, Kuramoto T, Serikawa T
    • Journal Title

      Vet Pathol 45(4)

      Pages: 586-591

    • Related Report
      2008 Final Research Report
  • [Journal Article] Functional polymorphisms in inbred rat strains and their allele frequencies in commercially available outbred stocks2008

    • Author(s)
      Kuramoto T, Nakanishi S, Serikawa T
    • Journal Title

      Physiol Genomics 33

      Pages: 205-211

    • Related Report
      2008 Final Research Report
  • [Journal Article] Establishment of thymoma-prone congenic rat strain, ACI.BUF/Mna-Tsr1/Tsr12008

    • Author(s)
      Matsuyama M, Kato K, Higo-Moriguchi K, Yamada T, Kuramoto T, Kuroda M
    • Journal Title

      J Cancer Res Clin Oncol 134(7)

      Pages: 789-792

    • Related Report
      2008 Final Research Report
  • [Journal Article] Evaluation of LEXF/FXLE rat recombinant inbred strains for the genetic dissection of complex traits2008

    • Author(s)
      Voigt B, Kuramoto T, Mashimo T, Tsurumi T, Sasaki Y, Hokao R, Serikawa T
    • Journal Title

      Physiol Genomics 32(3)

      Pages: 335-342

    • Related Report
      2008 Final Research Report
  • [Journal Article] Progress and prospects in rat genetics : a community view2008

    • Author(s)
      Aitman TJ, et al.
    • Journal Title

      Nature Genetics 40

      Pages: 516-522

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SNP and haplotype mapping for genetic analysis in the rat2008

    • Author(s)
      The STAR consortium
    • Journal Title

      Nature Genetics 40

      Pages: 560-566

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An ENU-induced mutant archive for gene targeting in rats.2008

    • Author(s)
      Mashimo T, et al.
    • Journal Title

      Nature Genetics 40

      Pages: 514-515

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Pancreatic metaplasia in the gastro-achlorhydria in WTC-dfk rat, a potassium channel Kcnql mutant.2008

    • Author(s)
      Kuwamura M, et al.
    • Journal Title

      Vet Pathol 45

      Pages: 586-591

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional polyiorphisms in inbred rat strains and their allele frequencies in commercially available outbred stocks.2008

    • Author(s)
      Kuramoto T, et al.
    • Journal Title

      Physiol Genomics 33

      Pages: 205-211

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of LEXF/FXLE rat recombinant inbred strainss for the genetic dissection of complx traits.2008

    • Author(s)
      Voigt B, Kuramoto T, et al.
    • Journal Title

      Physiol Genomics 32

      Pages: 335-342

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of LEXF/FXLE rat recombinant inbred strains for the genetic dissection of complex traits2008

    • Author(s)
      Voigt B, et. al.
    • Journal Title

      Physiological Genomics 32

      Pages: 335-342

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional polymorphisms in inbred rat strains and their allele frequencies in commercially available outbred2008

    • Author(s)
      Kuramoto T, et. al.
    • Journal Title

      Physiological Genomics (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Ca2^+ channel currents in cerebellar Purkinje cells of the ataxic groggy rat2007

    • Author(s)
      Tanaka K, Shirakawa H, Okada K, Konno M, Nakagawa T, Serikawa T, Kaneko S
    • Journal Title

      Neurosci Lett 426(2)

      Pages: 75-80

    • Related Report
      2008 Final Research Report
  • [Journal Article] Voltage-dependent calcium channel abnormalities in hippocampal CA3 neurons of spontaneously epileptic rats2007

    • Author(s)
      Yan HD, Ishihara K, Hanaya R, Kurisu K, Serikawa T, Sasa M
    • Journal Title

      Epilepsia 48(4)

      Pages: 758-764

    • NAID

      120000876126

    • Related Report
      2008 Final Research Report
  • [Journal Article] Absence-like and tonic seizures in Aspartoacylase/Attractin double-mutant mice2007

    • Author(s)
      Gohma H, Kuramoto T, Matalon R, Surendran S, Tyring S, Kitada K, Sasa M, and Serikawa T
    • Journal Title

      Exp Anim 56(2)

      Pages: 161-165

    • NAID

      130000068047

    • Related Report
      2008 Final Research Report
  • [Journal Article] The ataxic groggy rat has a missense mutation in the P/Q-type voltage gated Ca2+ channel <alpha>1A subunit gene and exhibits absence seizures2007

    • Author(s)
      Tokuda S, Kuramoto T, Tanaka T, Kaneko S, Takeuchi IK, Sasa M, and Serikawa T
    • Journal Title

      Brain Res 1133(1)

      Pages: 168-177

    • Related Report
      2008 Final Research Report
  • [Journal Article] Generation of rat offspring derived from cryopreserved spermatozoa in Japanese National Bioresources2007

    • Author(s)
      Kashiwazaki N, Seita Y, Naoi K, Takizawa A, Kuramoto T, and Serikawa T
    • Journal Title

      Reprod Fertil Dev 19(1)

      Pages: 124-125

    • Related Report
      2008 Final Research Report
  • [Journal Article] Absence-like and tonic seizures in Aspartoacylase/Attractin double-mutant mice.2007

    • Author(s)
      Gohma H, et al.
    • Journal Title

      Exp Anim (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The ataxic groggy rat has a missense mutation in the P/Q-type voltage gated Ca2+ channel <alpha>1A subunit gene and exhibits absence2007

    • Author(s)
      Tokuda S. et al.
    • Journal Title

      Brain Res

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Generation of rat offspring derived from cryopreserved spermatozoa in Japanese National Bioresources2007

    • Author(s)
      Kashiwazaki N et al.
    • Journal Title

      Reprod Fertil Dev 19 (1)

      Pages: 124-125

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A set of highly informative rat simple sequence length polymorphism (SSLP) markers and genetically defined rat strains2006

    • Author(s)
      Mashimo T, Voigt B, Tsurumi T, Naoi K, Nakanishi S, Yamasaki K, Kuramoto T, and Serikawa T
    • Journal Title

      BMC Genetics 7

      Pages: 19-19

    • NAID

      120004770256

    • Related Report
      2008 Final Research Report
  • [Journal Article] a rat model for extensive investigations of Kcnq1 functions2006

    • Author(s)
      Gohma H, Kuramoto T, Kuwamura M, Okajima R, Tanimoto N, Yamasaki K, Nakanishi S, Kitada K, Makiyama T, Akao M, Kita T, Sasa M, and Serikawa T WTC deafness Kyoto (dfk)
    • Journal Title

      Physiol Genomics 24(3)

      Pages: 198-206

    • Related Report
      2008 Final Research Report
  • [Journal Article] Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat2006

    • Author(s)
      Mori M, Li G, Abe I, Nakayama J, Guo Z, Sawashita J, Ugawa T, Nishizono S, Serikawa T, Higuchi K, and Shumiya S
    • Journal Title

      J Clin Invest 116

      Pages: 395-404

    • Related Report
      2008 Final Research Report
  • [Journal Article] A set of highly informative rat simple sequence length polymorphism (SSLP) markers and genetically defined rat strains.2006

    • Author(s)
      Mahimo et al.
    • Journal Title

      BMC Genet 7

      Pages: 19-19

    • Related Report
      2006 Annual Research Report
  • [Journal Article] WTC deafness Kyoto (dfk) : a rat model for extensive investigations of Kcngl functions2006

    • Author(s)
      Gohma et al.
    • Journal Title

      Physiol Genomics 24(3)

      Pages: 198-198

    • Related Report
      2006 Annual Research Report
  • [Presentation] Genetic dissection of the LEXF/FXLE recombinant inbred strains.2008

    • Author(s)
      Kuramoto T, Voigt B, Mashimo T, Sasaki Y, Hokao R, Serikawa T.
    • Organizer
      13th International SHR symposium
    • Place of Presentation
      プラハ
    • Year and Date
      2008-06-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] ラット機能多型のジェノタイピング2008

    • Author(s)
      中西聡, 庫本高志, 芹川忠夫
    • Organizer
      第55回日本実験動物学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] ラツトLEXF/FXLEリコンビナント近交系を用いたQTL解析2008

    • Author(s)
      庫本高志, ら
    • Organizer
      第55回日本実験動物学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] 脂質代謝・糖質代謝におけるラットリソースの活用 シンポジウム 脂質代謝・糖質代謝を制御するメタボリックセンサーの分子機構2008

    • Author(s)
      庫本高志
    • Organizer
      日本農芸化学会2008年度大会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Genetic dissection of the LEXF/FXLE recombinant inbred strains2008

    • Author(s)
      Kuramoto T, Voigt B, Mashimo T, Sasaki Y, Hokao R, Serikawa T
    • Organizer
      13th International SHR symposium
    • Place of Presentation
      Prague, Czech Republic
    • Related Report
      2008 Final Research Report
  • [Presentation] ラット機能多型のジェノタイピング2008

    • Author(s)
      中西聡、庫本高志、芹川忠夫
    • Organizer
      第55回 日本実験動物学会総会
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本産野生由来DOBラットの遺伝的特徴2008

    • Author(s)
      岡島涼子、庫本高志、真下知士、鶴見東志子、Zhang Zouming、目加田和之、夏目明香、町田侑平、織田銑一、芹川忠夫
    • Organizer
      第55回 日本実験動物学会総会
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Presentation] ラットLEXF/FXLEリコンビナント近交系を用いたQTL解析2008

    • Author(s)
      庫本高志1、北斗美留賀1、真下知士1、鶴見東志子1、佐々木敬幸2、外尾亮治2、芹川忠夫
    • Organizer
      第55回 日本実験動物学会総会
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Presentation] Genetic dissection of the LEXF/FXLE recombinant inbred strains: A SNP based QTL study.2007

    • Author(s)
      Voigt B, et. al.
    • Organizer
      The 2007 meeting on Rat Genomics & Models
    • Place of Presentation
      Cold Spring Harbor
    • Year and Date
      2007-12-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] Genetic dissection of the LEXF/FXLE recombinant inbred strains : A SNP based QTL study2007

    • Author(s)
      Voigt B, Mashimo T, Kuramoto T, Takizawa A, Yamasaki K, Nakanishi S, Serikawa T
    • Organizer
      The 2007 meeting on Rat Genomics & Models
    • Place of Presentation
      Cold Spring Harbor, New York, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] ラット近交系におけるRT1領域の遺伝子型プロファイル2007

    • Author(s)
      高木弓枝、庫本高志、鶴見東志子、中西 聡、真下知士、増井則夫、芹川忠夫
    • Organizer
      第54回 日本実験動物学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 毛胞と乳腺の発育不全を示す Sparse and wavy hair ラットの原因遺伝子の同定2007

    • Author(s)
      庫本高志、芹川忠夫
    • Organizer
      第54回 日本実験動物学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ラットFXLE/LEXFリコンビナント近交系を用いた量的形質の遺伝解析2006

    • Author(s)
      庫本高志、Birger Voigt、鶴見東志子、真下知士、佐々木敬幸、外尾亮治、芹川忠夫
    • Organizer
      第23回 日本疾患モデル学会
    • Place of Presentation
      渋川
    • Year and Date
      2006-11-30
    • Related Report
      2008 Final Research Report
  • [Presentation] Recombinant Inbred Strains & Genetic Dissection of Phenotypes2006

    • Author(s)
      Voigt B, Kuramoto T, Tsurumi T, Mashimo T, Sasaki Y, Hokao R, Serikawa T
    • Organizer
      XVIth International Workshop on Rat Genetic Systems
    • Place of Presentation
      Melbourne
    • Related Report
      2008 Final Research Report
  • [Presentation] The ataxic groggy rat has a missense mutation in the P/Q-type voltage gated Ca2+ channel a1A subunit gene and exhibits absence seizures2006

    • Author(s)
      Tokuda S, Kuramoto T, Tanaka K, Kaneko K, Takeuchi I, Sasa M, Serikawa T
    • Organizer
      XVIth International Workshop on Rat Genetic Systems
    • Place of Presentation
      Melbourne
    • Related Report
      2008 Final Research Report
  • [Presentation] The LEXF/FXLE rat recombinant inbred strain set : a newly enhanced tool for genetic dissection of complex traits2006

    • Author(s)
      Kuramoto T, Voigt B, Tsurumi T, Mashimo T, Sasaki Y, Hokao R, Serikawa T
    • Organizer
      The 2nd Asian Federation of Laboratory Animal Science Associations, Jeju
    • Place of Presentation
      Korea
    • Related Report
      2008 Final Research Report
  • [Presentation] ラット FXLE/LEXF RI系統セットの活用2006

    • Author(s)
      庫本高志、ビルガーフォークト、直井国子、山崎賢一、中西 聡、鶴見東志子、真下知士、左近上博司、西森司雄、外尾亮治、芹川忠夫
    • Organizer
      第20回 日本糖尿病動物研究会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 電位依存性カリウムチャネルKcnq1遺伝子変異ラット(deafness Kyotoラット)2006

    • Author(s)
      庫本高志、郷間宏史、桑村 充、中西 聡、北田一博、赤尾昌治、牧山 武、北 徹、笹 征史、芹川忠夫
    • Organizer
      第53回 日本実験動物学会総会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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