Analysis of the Molecular Pathology for the Salidonmide Syndrome

• Project/Area Number: 18591150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: SAKAI Norio Osaka University, Graduate School of Medicine, Associate Professor (30314313)
• Co-Investigator(Kenkyū-buntansha): TANIIKE Masto Osaka Univetsty, Graduate School of Medicine, Specially Appointed Professor (30263289)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: salidomide / teratogen / Roberts syndrome / ESCO2 / ESCO2 / 催奇性因子

Research Abstract

Salidomide is a medicine which has anti-immune effect and anti-inflamation effect. Recently this medicine is applied for the treatment for several diseases. However it is also well-known to show the strong teratogenic effect for the embryo which is called Salidomide syndrome, which mechanism is still unclear. We planed the research to disclose the mechanism of the teratogenic effect of the salidomide. We have experience the molecular cloning of Roberts syndrome which is human genetic disease with phenotype of phocomelia, which resemble to the limb phenotype of salidomide syndrome. We analyze the salidomide died on the expression level of possible target genes using cultured cell line. We found suppressed expression of ESCO2 which is defect in Roberts syndrome which might suggest the part of mechanism of salidomide syndrome. Other research effort proved the cellular biological characteristics of Roberts patient lymphoblasts. They are sensitive to the mitomycine C than normal lymphoblast and has problem in spindle checkpoint. These result might lead the disclosure of salidomide side effect and suggest the treatment to inhibit the teratogenic effect

Research Products

• [Journal Article] Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone. (2008)
  • Author(s): Shimotori M, Maruyama H, Sakai N(9), Gejyo F(31)
  • Journal Title: Hum Mutat 29 Pages: 331-40
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone (2008)
  • Author(s): Shimotori, M, Maruyama, H, Sakai, N(9), Gejyo, F(31)
  • Journal Title: Hum Mutat 29 Pages: 331-40
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of nuclear factor I transcription/replication factor in the early stage of chondrocytic differentiation. (2007)
  • Author(s): Uchihashi T, Kimata M, Tachikawa K, Koshimizu T, Okada T, Ihara-Watanabe M, Sakai N, Kogo M, Ozono K, Michigami T
  • Journal Title: Bone 41 Pages: 1025-35
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Involvement of nuclear factor I transcription/replication factor in the early stage of chondrocytic differentiation (2007)
  • Author(s): Uchihashi, T, Kimata, M, Tachikawa, K, Koshimizu, T, Okada, T, Ihara-Watanabe, M, Sakai, N, Kogo, M, Ozono, K, Michigami, T
  • Journal Title: Bone 41 Pages: 1025-35
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The luminal domain participates in the endosomal trafficking of the cation-independent mannose 6-phosphate receptor (2006)
  • Author(s): Waguri S, Tomiyama Y, Ikeda H, Hida T, Sakai N, Taniike M, Ebisu S, Uchiyama Y
  • Journal Title: Exp Cell Res 312 (20) Pages: 4090-4107
• [Journal Article] Six novel mutations detected in GALC gene in 17 Japanese patients with Krabbe disease and new genotype-phenotype correlation (2006)
  • Author(s): Xu C, Sakai N, Taniike M, Inui, Ozono K
  • Journal Title: J Hum Genet 51(6) Pages: 548-554
  • NAID: 10017608409
• [Journal Article] Characterization of the sensitivity of lymphoblastoid cell lines to various stress agents in Roberts syndrome (2006)
  • Author(s): Gordillo M, Vega H, Sakai N, Tsukamoto H, Ozono K, Inui K
  • Journal Title: Med J Osaka Univ 49(1-4) Pages: 29-41
• [Journal Article] Novel mutation of gene coding for glial fibrillary acidic protein in a Japanese patient with Alexander disease (2006)
  • Author(s): Kawai M, Sakai N, Miyake S, Tsukamoto H, Akagi M, Inui K, Mushiake S, Taniike M, Ozono K
  • Journal Title: Brain Dev 28(1) Pages: 60-62
  • NAID: 10017319316
• [Presentation] Mutation analysis of GNPTAB gene in 24 Japanese Mucolipidosis II and III patients. (2007)
  • Author(s): Otomo T, Muramatsu T, Inui K, Yorifuji T, Nakabayashi H, Ohura T, Yoshino M, Tanaka A, Okuyama T, Ozono K, sakai N
  • Organizer: SSIEM 2007 Annual symposium,
  • Place of Presentation: Germany, Hamburg
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Mutation analysis of GNPTAB gene in 24 Japanese Mucolipidosis II and III patients (2007)
  • Author(s): Otomo, T, Muramatsu, T, Inui, K, Yorifuji, T, Nakabayashi, H, Ohura, T, Yoshino, M, Tanaka, A, Okuyama, T, Ozono, K, Sakai, K
  • Organizer: SSIEM 2007 Annual symposium
  • Place of Presentation: Germany, Hamburg
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Mutation analysis of GNPTAB gene in 24 Japanese Mucolipidosis II and III patients. (2007)
  • Author(s): Otomo T, Sakai N(11)
  • Organizer: SSIEM 2007 Annual symposium,
  • Place of Presentation: Hamburg、ドイツ