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2010 Fiscal Year Annual Research Report

拒食症の感受性遺伝子の網羅的同定と機能解析による発症カスケードの解明

Research Project

Project/Area Number 19101008
Research InstitutionTokai University

Principal Investigator

猪子 英俊  東海大学, 医学部, 教授 (10101932)

Keywords摂食障害 / マイクロサテライト / 感受性遺伝子 / シナプトガミン / NETO / シンタキシン / 酵母ツーハイブリッド法 / 疾患モデルマウス
Research Abstract

ゲノムワイドなマイクロサテライト解析により、摂食障害の感受性遺伝子として同定したSYT12とNRO1の両者について、それぞれ我々が改良した酵母Two Hybrid法を行い、両者ともシナプス小胞開口放出・リサイクリングに関係しているSH3GL3とSyntaxin8と相互作用していることが、明らかとなった。これらの相互作用は、FRET、BRET、ルシフェラーゼ、βガラクトシダーゼ、DHFR等を用いたPCAによって神経細胞においても確認された。これらの事実は、摂食障害がシナプスにおける神経伝達物質の代謝による異常によって発症することを示唆する。これらの結果からシナプス小胞開口放出に関係しているSyntaxin8に対し、構造的な立場から摂食障害の創薬の標的としての低分子リガンド探索を考えている。尚、SYT12が2型糖尿病の感受性遺伝子であるSH3GL3とも相互作用することが実証され、摂食行動と糖尿病との関連が推測され興味深い。一方、摂食障害感受性遺伝子のマウス変異体の解析として、SYT12、CNTN5、NETO1の各々のマウス変異個体、及び、これらの掛け合わせによって得られるダブル・トリプル変異個体を用いて、これらの遺伝子の変異が及ぼす効果を検討したが、通常の生理学的・生化学的データの収集や、行動解析に加えて、ストレス下における行動異常について検索してが、現在までのところ正常マウスとの相違は観察されなかった。

  • Research Products

    (32 results)

All 2011 2010

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (8 results)

  • [Journal Article] Which CIDE are you on? Apoptosis and energy metabolism2011

    • Author(s)
      Yonezawa T, Kurata R, Kimura M, Inoko H
    • Journal Title

      Mol Biosyst

      Volume: 7 Pages: 91-110

    • Peer Reviewed
  • [Journal Article] Meta-Analysis Confirms the LCE3C-LCE3B Deletion as a Risk Factor for Psoriasis in Several Ethnic Groups and Finds Interaction with HLA-Cw62011

    • Author(s)
      Riveira-Munoz E, He SM, Es caramis G, Stuart PE, Huffmeier U, Lee C, Kirby B, Oka A, Giardina E, Liao W, Bergboer J, Kainu K, de Cid R, Munkhbat B, Zeeuwen PL, Armour JA, Poon A, Mabuchi T, Ozawa A, Zawirska A, Burden AD, Barker JN, Capon F, Traupe H, Sun LD, Cui Y, Yin XY, Chen G, Lim HW, Nair RP, Voorhees JJ, Tejasvi T, Pujol R, Munkhtuvshin N, Fischer J, Kere J, Schalkwijk J, Bowcock A, Kwok PY, Novelli G, Inoko H, Ryan AW, Trembath RC, Reis A, Zhang XJ, Elder JT, Estivill X
    • Journal Title

      J Invest Dermatol

      Volume: 131 Pages: 1105-1109

    • Peer Reviewed
  • [Journal Article] Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT Bone2011

    • Author(s)
      Murase M, Nishida T, Onizuka M, Inamoto Y, Sugimoto K, Imahashi N, Murata M, Miyamura K, Kodera Y, Inoko H, Naoe T
    • Journal Title

      Marrow Transplant

      Volume: Dec 20(epub) Pages: 1-6

    • Peer Reviewed
  • [Journal Article] NFKBIL1 confers resistance to experimental autoimmune arthritis through the regulation of dendritic cell functions.2011

    • Author(s)
      Chiba T, Matsuzaka Y, Warita T, Sugoh T, Miyashita K, Tajima A, Nakamura M, Inoko H, Sato T, Kimura M
    • Journal Title

      Scand J Immunol

      Volume: 73 Pages: 478-485

    • Peer Reviewed
  • [Journal Article] Primordial linkage of β2-microglobulin to the MHC2011

    • Author(s)
      Ohta Y, Shiina T, Lohr RL, Hosomichi K, Pollin TI, HeistEJ, Suzuki S, Inoko H, Flajnik MF
    • Journal Title

      J Immunol

      Volume: 186 Pages: 3563-3567

    • Peer Reviewed
  • [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population.2011

    • Author(s)
      Sato M, Kawagoe T, Meguro A, Ota M, Katsuyama Y, Ishihara M, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, OhnoS, Inoko H, Mizuki N
    • Journal Title

      Mol Vis

      Volume: 17 Pages: 731-736

    • Peer Reviewed
  • [Journal Article] Targeted transgenesis through pronuclear injection of improved vectors into in vitro fertilized eggs.2011

    • Author(s)
      Ohtsuka M, Miura H, Nakaoka H, Kimura M, Sato M, Inoko H.
    • Journal Title

      Transgenic Res

      Volume: Mar 25 Pages: 1-2

    • Peer Reviewed
  • [Journal Article] Individuals susceptible to lung adenocarcinoma defined by combined HLA-DQA1 and TERT genotypes.2010

    • Author(s)
      Kohno T, Kunitoh H, Shimada Y, Shiraishi K, Ishii Y, Goto K, Ohe Y, Nishiwaki Y, Kuchiba A, Yamamoto S, Hirose H, Oka A, Yanagitani N, Saito R, Inoko H, Yokota J
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 834-841

    • Peer Reviewed
  • [Journal Article] Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans.2010

    • Author(s)
      Kulski JK, Shigenari A, Inoko H
    • Journal Title

      Immunogenetics

      Volume: 62 Pages: 211-230

    • Peer Reviewed
  • [Journal Article] Mapping of susceptibility locus for endometriosis within the HLA region using microsatellite markers in Japanese women.2010

    • Author(s)
      Matsuzaka Y, Kikuti YY, Izumi S, Suzuki T, Cai LY, Goya K, Inoko H, Makino T, Kulski JK, Kimura M
    • Journal Title

      Tissue Antigens

      Volume: 75 Pages: 65-67

    • Peer Reviewed
  • [Journal Article] Anti-human very late antigen-alpha4 (CD49d) monoclonal antibody (BU49) cross-reacts with the canine B-cell leukemia cell line GL-1, resulting in the induction of homotypic cell aggregation.2010

    • Author(s)
      Ikewaki N, Nakaichi M, Mizuno T, Takamura N, Tokunaga J, Ogata K, Inoko H, Otsu R
    • Journal Title

      Cell Immunol

      Volume: 263 Pages: 55-64

    • Peer Reviewed
  • [Journal Article] Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma.2010

    • Author(s)
      Murakami K, Meguro A, Ota M, Shiota T, Nomura N, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, Iwase A, Ohno S, Inoko H, Mizuki N
    • Journal Title

      Mol Vis

      Volume: 16 Pages: 462-466

    • Peer Reviewed
  • [Journal Article] Impact of highly conserved HLA haplotype on acute graft-versus-host disease.2010

    • Author(s)
      Morishima S, Ogawa S, Matsubara A, Kawase T, Nannya Y, Kashiwase K, Satake M, Saji H, Inoko H, Kato S, Kodera Y, Sasazuki T, Morishima Y
    • Journal Title

      Blood

      Volume: 115 Pages: 4664-4670

    • Peer Reviewed
  • [Journal Article] Genome-wide association study of normal tension glaucoma : common variants in SRBD1 and ELOVL5 contribute to disease susceptibility.2010

    • Author(s)
      Writing Committee for the Normal Tension Glaucoma Genetic Study Group of Japan Glaucoma Society, Meguro A, Inoko H, Ota M, Mizuki N, Bahram S
    • Journal Title

      Ophthalmology

      Volume: 117 Pages: 1331-1338

    • Peer Reviewed
  • [Journal Article] Polymorphic major histocompatibility complex class II Alu insertions at five loci and their association with HLA-DRB1 and -DQB1 in Japanese and Caucasians.2010

    • Author(s)
      Kulski JK, Shigenari A, Shiina T, Inoko H
    • Journal Title

      Tissue Antigens

      Volume: 76 Pages: 35-47

    • Peer Reviewed
  • [Journal Article] Flow cytometric identification of CD93 expression on naive T lymphocytes (CD4(+)CD45RA (+) cells) in human neonatal umbilical cord blood.2010

    • Author(s)
      Ikewaki N, Yamao H, Kulski JK, Inoko H
    • Journal Title

      J Clin Immunol

      Volume: 30 Pages: 723-733

    • Peer Reviewed
  • [Journal Article] Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci.2010

    • Author(s)
      Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
    • Journal Title

      Nature Genet

      Volume: 42 Pages: 703-706

    • Peer Reviewed
  • [Journal Article] Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.2010

    • Author(s)
      Michikawa Y, Suga T, Ishikawa A, Hayashi H, Oka A, Inoko H, Iwakawa M, Imai T
    • Journal Title

      BMC Med Genet

      Volume: 11 Pages: 123

    • Peer Reviewed
  • [Journal Article] TRIM39 and RNF39 are associated with Behcet's disease independently of HLA-B*51 and -A*262010

    • Author(s)
      Kurata R, Nakaoka H, Tajima A, Hosomichi K, Shiina T, Meguro A, Mizuki N, Ohono S, Inoue I, Inoko H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 401 Pages: 533-537

    • Peer Reviewed
  • [Journal Article] Pronuclear injection-based mouse targeted transgenesis for reproducible and highly efficient transgene expression.2010

    • Author(s)
      Ohtsuka M, Ogiwara S, Miura H, Mizutani A, Warita T, Sato M, Imai K, Hozumi K, Sato T, Tanaka M, Kimura M, Inoko H
    • Journal Title

      Nucleic Acids Res

      Volume: 38 Pages: e198

    • Peer Reviewed
  • [Journal Article] Mitochondrial DNA diversity among three subpopulations of cynomolgus macaques (Macaca fascicularis) originating from the Indochinese region.2010

    • Author(s)
      Shiina T, Tanaka K, Katsuyama Y, Otabe K, Sakamoto K, Kurata M, Nomura M, Yamanaka H, Nakagawa H, Inoko H, Ota.M
    • Journal Title

      Exp Anim

      Volume: 59 Pages: 567-578

    • Peer Reviewed
  • [Journal Article] Genotyping HLA-DRB1 and HLA-DQB1 alleles in Japanese patients with normal tension glaucoma.2010

    • Author(s)
      Suzuki M, Meguro A, Ota M, Nomura E, Kato T, Nomura N, Kashiwagi K, Mabuchi F, lijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, Iwase A, Ohno S, Inoko H, Mizuki N
    • Journal Title

      Mol Vis

      Volume: 16 Pages: 1874-1879

    • Peer Reviewed
  • [Journal Article] Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients2010

    • Author(s)
      Onizuka M, Kunii N, Toyosaki M, Machida S, Ohgiya D, Ogawa Y, Kawada H, Inoko H, Ando K
    • Journal Title

      Bone Marrow Transplant

      Volume: Nov 22(epub) Pages: 1-5

    • Peer Reviewed
  • [Journal Article] Association analysis of Toll-like receptor 7 gene polymorphisms and Behcet's disease in Japanese patients2010

    • Author(s)
      Sada T, Ota M, Katsuyama Y, Meguro A, Nomura E, Uemoto R, Nishide T, Okada E, Ohno S, Inoko H, Mizuki N
    • Journal Title

      Hum Immunol

      Volume: 72 Pages: 269-272

    • Peer Reviewed
  • [Presentation] 次世代シークエンサーを用いたHLA領域のリシークエンシングによる多型解析2011

    • Author(s)
      猪子英俊
    • Organizer
      第9回日本組織適合性学会近畿地方会特別講演
    • Place of Presentation
      大阪
    • Year and Date
      2011-02-05
  • [Presentation] HLAと薬物副作用2011

    • Author(s)
      猪子英俊
    • Organizer
      PGxデータサイエンスコンソーシャム講演
    • Place of Presentation
      東京田辺製薬
    • Year and Date
      2011-02-02
  • [Presentation] HLAの多型と疾患感受性2010

    • Author(s)
      猪子英俊
    • Organizer
      日本癌病態治療研究会学術講演会
    • Place of Presentation
      東京都市センターホテル
    • Year and Date
      2010-11-04
  • [Presentation] 摂食障害のゲノム解析GWAS(Genome-Wide Association Studies)と今後のWhole Genome Sequencing2010

    • Author(s)
      猪子英俊
    • Organizer
      摂食障害遺伝子研究協力者会議
    • Place of Presentation
      東京
    • Year and Date
      2010-10-15
  • [Presentation] 健康と遺伝子2010

    • Author(s)
      猪子英俊
    • Organizer
      ワールドハートデイ神戸
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2010-09-26
  • [Presentation] 漢方医学教育養成のための神奈川県4大学連携型によるシステムの構築2010

    • Author(s)
      猪子英俊
    • Organizer
      第2回福島県立大東洋医学研究会
    • Place of Presentation
      福島県立医科大学
    • Year and Date
      2010-09-10
  • [Presentation] 身体はゲノムの単なる乗り物か?2010

    • Author(s)
      猪子英俊
    • Organizer
      第67回日本臨床検査医学会関東甲信越支部例会/第21回神奈川県臨床検査医学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2010-05-29
  • [Presentation] ゲノムワイドな相関解析によるありふれた疾患の遺伝子の同定とゲノム創薬2010

    • Author(s)
      猪子英俊
    • Organizer
      第79回神奈川腎研究会
    • Place of Presentation
      北里大学
    • Year and Date
      2010-05-15

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Published: 2012-07-19  

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