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
| Project/Area Number |
14370686
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
矯正・小児・社会系歯学
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| Research Institution | Hokkaido University |
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Principal Investigator |
OGUCHI Haruhisa Hokkaido Univ., Grad.School of Dent.Med., Prof., 大学院・歯学研究科, 教授 (30124689)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | amelogenesis imperfecta / enamelin / amelogenin / differentiation / mutation / tooth germ / exon / intron |
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| 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.
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