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2003 Fiscal Year Final Research Report Summary

Identification of a novel mutation in the amelogenesis-related genes in Japanese families affected with amelogenesis imperfecta and an approach toward gene therapy

Research Project

Project/Area Number 14370686
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 矯正・小児・社会系歯学
Research InstitutionHokkaido University

Principal Investigator

OGUCHI Haruhisa  Hokkaido Univ., Grad.School of Dent.Med., Prof., 大学院・歯学研究科, 教授 (30124689)

Co-Investigator(Kenkyū-buntansha) MITOME Masato  Hokkaido Univ., Grad.School of Dent.Med., Instr., 大学院・歯学研究科, 助手 (50261318)
SHIRAKAWA Tetsuo  Hokkaido Univ., Grad.School of Med., Asso.Prof., 医学部・歯学部附属病院, 助教授 (00187527)
ARIGA Tadashi  Hokkaido Univ., Grad.School of Dent.Med., Asso.Prof., 大学院・医学研究科, 客員助教授 (60322806)
KIKUIRI Takashi  Hokkaido Univ., Grad.School of Dent.Med., Instr., 大学院・歯学研究科, 助手 (10322819)
Project Period (FY) 2002 – 2003
Keywordsamelogenesis imperfecta / enamelin / amelogenin / differentiation / mutation / tooth germ / exon / intron
Research Abstract

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders characterized by the defects of tooth enamel formation.
1) We performed molecular genetic studies for a Japanese family with a possible autosomal dominant form of Al, and found a novel mutation in the enamelin gene. The mutation detected in the affected brothers and their father was a heterozygous single-G deletion within a series of 7G residues at the exon 9-intion 9 boundary of the enamelin gene. The enamelin gene mutation was not detected in other unaffected family members or control individuals suggesting that the mutation in the enamelin gene is responsible for an autosomal dominant hypoplastic form of AI.
2) We studied a Japanese family that exhibits inherited abnormality in tooth formation characterized by teeth with vertical grooves (female) and small brownish teeth (male), and found a mutation in the amelogenin gene located in the p22.1-22.3 region of the X chromosome. Mutation analysis revealed a C to G point mutation in exon 5 of the amelogenin gene, which would substitute arginine for proline^<52>. This substitution co-segregated with the tooth abnormality in the affected family members and the locus encoding proline^<52> highly conserved in other mammals. This result indicates that the mutation detected in this Japanese family is responsible for the X-linked AI.
3) We also tested a novel retroviral vector GcsapM-ADA for its ability to transduce genes in hematopoietic cells and found this method to be beneficial to patients.
4) The regulatory effects of the macrophage migration inhibitory factor (MIF) on osteoclast formation were examined and we found that MIF inhibits formation of mature osteoclasts by preventing the multinucleation process.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kida M.: "Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary."Journal of Dental Research. 81. 738-742 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉田 重慶: "血液幹/前駆細胞を標的とするADA欠損症における遺伝子治療基礎研究:至適化遺伝に導入法での遺伝子導入効率および遺伝に導入の骨髄再構築能の検討"北海道歯学雑誌. 23. 113-122 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田畑 太: "破骨細胞分化に対するマクロファージ遊走阻止因子(MIF)の影響について-マウス骨髄細胞ならびに骨芽細胞の共存培養条件化におけるMIFの作用-"小児科歯科学雑誌. 41. 860-868 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kida, M.: "The First Report of a Japanese Family with Autosomal-dominant Amelogenesis Imperfecta Caused by an Enamelin Gene Mutation."Archives of comparative Biology of Tooth Enamel. 8. 72-75 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Horiuchi, K.: "Teacher Collins Syndrome with Craniosynostosis, Occlusion of Choanae and Esophageal Regurgitation caused by Nonsense Mutation in the TCOF1 : A New Variant."American Journal of Medical Genetics. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kida M.: "Single-base Deletion at the Exon-intron Junction of the Enamelin Gene Causes an Autosomal-dominant Hypoplastic From of Amelogenesis Imperfecta."Journal of Dental Research. 81. 738-742 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J.: "Preclinical studies of stem/progenitor cell-directed gene therapy for ADA-deficiency : evaluation of gene transduction efficiency and repopulating abilities in ex vivo-manipulated CD34+ cells."Hokkaido Journal of Dental Science (in Japanese with English abstract). 23. 113-122 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tabata, F.: "The Influence of Macrophage Migration Inhibitory Factor on Osteoclast Formation in Coculture."The Japanese Journal of Pediatric Dentistry (in Japanese with English abstract). 41. 860-868 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kida, M.: "The First Report of a Japanese Family with Autosomal-dominant Amelogenesis Imperfecta Caused by an Enamelin Gene Mutation."Archives of Comparative Biology of Tooth Enamel. 8. 72-75 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Horiuchi, K.: "Treacher Collins Syndrome with Craniosynostosis, Occlusion of Choanae and Esophageal Regurgitation caused by Nonsense Mutation in the TCOF1 : A New Variant."American Journal of Medical Genetics. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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