Research on the common molecular pathology for autism

• Project/Area Number: 18390301
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Jichi Medical University
• Principal Investigator: MOMOI Mariko Jichi Medical University, 医学部, 教授 (90166348)
• Co-Investigator(Kenkyū-buntansha): YAMAGATA Takanori 自治医科大学, 医学部, 准教授 (00239857) ; MORI Masato 自治医科大学, 医学部, 講師 (10337347) ; NOZAKI Yasuyuki 自治医科大学, 医学部, 助教 (90281295) ; GOTO Tamako 自治医科大学, 医学部, 助教 (40364509) ; KUWAJIMA Mari 自治医科大学, 医学部, 研究生 (30398515)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,740,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥2,340,000); Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
• Keywords: 自閉性障害 / シナプス形成 / CADM1 / FOXP2 / 自閉症 / secretin受容体 / ノックインマウス / 遺伝子発現解析 / 発現アレイ解析 / WNT

Research Abstract

自閉性障害の分子機構の解明のために、原因遺伝子検索、遺伝子発現プロファイリング、遺伝子改変マウスによる分子病態の解析を実施した。ヒト変異を有するFOXP2遺伝子改変マウスのhomozygoteでは変異遺伝子産物は核に輸送されず細胞質内に停留する分子病態を確認した。さらに、シナプス接着蛋白遺伝子であるCADM1に2個の変異を検出し、遺伝子欠損マウスにおける社会性行動異常を確認した。罹患者の末梢血球における遺伝子発現解析では、GPCR群の発現が有意に増加しており、原因分子病態の結果を反映すると考えられた。また、一部の罹患者において、MECP2で制御を受けるDLX5の発現が増加していた。同様に制御されるDLX6には罹患同胞にミスセンス変異を認めたことから、これらの遺伝子が病態に関与する可能性を示唆した。

Research Products

• [Journal Article] Expression analysis and mutation detection of DLX5 and DLX6 in autism. (2009)
  • Author(s): Nakajima N, Yamagata T, MoriM, Kuwajima M, Suwa K, Momoi MY.
  • Journal Title: Brain Dev doi:10 Pages: 1016-1016
  • NAID: 10027212757
  • Peer Reviewed
• [Journal Article] Expression analysis and mutation detection of DLX5 and DLX6 in autism. (2009)
  • Author(s): Nakashima, N, Yamagata, T, Mori M, Kuwajima M, Suwa K, MOMOI MY.
  • Journal Title: Brain & Development Feb3 (E-pub)
  • NAID: 10027212757
  • Peer Reviewed
• [Journal Article] Mutations in the gene encoding CADM1 are associated with autism spectrum disorder. (2008)
  • Author(s): Zhiling Y, Fujita E, Tanabe Y, Yamagata T, Momoi T, Momoi MY.
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 926-929
  • Peer Reviewed
• [Journal Article] Ultrasonic vocaliz ation impairment of FOXP2 (R552H) knockin mice related to speech-language disorder and abnormality of Pukinje cells. (2008)
  • Author(s): Fijita E, Tanabe Y, Shiota A, Ueda M, Suwa K, Momoi MY, Momoi T.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 3117-3122
  • Peer Reviewed
• [Journal Article] Mutations in the gene encoding CADM1 are associated with autism spectrum disorder. (2008)
  • Author(s): Zhiling Y, Fujita E, Tmomoi anabe Y, Yamagata T, k, Momoi T, Momoi MY.
  • Journal Title: Biochem Biophys, Res Commun. 377 Pages: 926-9
  • Peer Reviewed
• [Journal Article] Ultrasonic vocalization impairment of Foxp2(R552)knockin mice related to speech-language disorder and abnormality of Purkinje cells. (2008)
  • Author(s): Fujita E, Tanabe Y, Shiota A, Ueda M, Suwa K, Momoi MY, Momoi T.
  • Journal Title: Proc Natl Acad Soi USA 105 Pages: 3117-22
  • Peer Reviewed
• [Journal Article] Ultrasonic vocalization ompairment of FOXP2 knockin mice related to speech/language disorder and abnormality of Purkinje cells. (2008)
  • Author(s): Fujita E, Tanabe Y, Shiowa A, et. al.
  • Journal Title: Proc Natl Acad Sci, USA 105 Pages: 3117-3122
  • Peer Reviewed
• [Journal Article] Intracellular dist ribution of a speech/language disorder associated FOXP2 mutant. (2007)
  • Author(s): Mizutani A, Matsuzaki A, Momoi MY,Fujita E, Tanabe Y, Momoi T.
  • Journal Title: Biochem Biopys Res Commun 353 Pages: 869-874
  • Peer Reviewed
• [Journal Article] Intracellular distribution of a speech/language disorder associated with FOXP2 mutant. (2007)
  • Author(s): Mizutani A, Matsuzaki A, Molmoi MY, et. al.
  • Journal Title: Boichem Biophys Res Commun 353 Pages: 869-874
  • Peer Reviewed
• [Journal Article] Intracellular distribution of a speech/language disorder associated FOXP2 mutant. (2007)
  • Author(s): Mizutani A, Matsuzaki A, F, Momoi MY, Ujita E, Tanabe Y, Momoi T.
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 869-874
• [Journal Article] Secretin receptor deficient mice exh ibited impaired synaptic plasticity and social behavior (2006)
  • Author(s): Nishijima I, Yamagata T, Spencer Cm,Weeber EJ, Alekseyenko O, Sweatt JD, Momoi MY, et al.
  • Journal Title: Hum mol Genet 15 Pages: 3241-3250
  • Peer Reviewed
• [Journal Article] A. Secretin receptor-deficient mice exhibit impaired synaptic plasticity and social behavior. (2006)
  • Author(s): Nishijima I, Yamagata T, Soencer CM, Weber EJ, Alekseyenko O, Seat JD, Momoi MY, Ito M, Armstrong DL, Nelson DL, Oaylor R, Bradley A.
  • Journal Title: Hum Mol Genet 15 Pages: 3241-3250
• [Presentation] (2008)
  • Author(s): USA American Academy of Human Genetics Branch
  • Organizer: International Autism Research meeting
• [Presentation] (2007)
  • Author(s): USA American Academy of Human Genetics Branch
  • Organizer: International Autism Research meeting