| Project/Area Number |
13557177
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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 | 展開研究 |
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| Research Field |
Surgical dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima Univ. Graduate Scho. Of Biomed. Sci., Professor, 大学院・医歯薬学総合研究科, 教授 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Hidemi Hiroshima Univ. Graduate Scho. Of Biomed. Sci., Professor, 大学院・医歯薬学総合研究科, 教授 (40161765)
KOBAYASHI Masashi Hiroshima Univ. Graduate Scho. Of Biomed. Sci., Research Associate, 大学院・医歯薬学総合研究科, 助手 (30346506)
坂本 哲彦 広島大学, 歯学部, 助手 (70294593)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2001: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | FGFRs / patched / EXT1, 2 / Tie-2 / Gene Diagnosis / Craniosyostosis / venous malformations / nevoid basal cell carcinoma syndrome / 頭蓋早期癒合症(FGFR1,FGFR2) / 外骨症(EXT1、EXT2) |
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| Research Abstract |
Mutations in receptors have been linked to an increasing number of inherited human disease syndromes affecting oral-craniofacial functions. Both gain-of-function mutations resulting in constitutive receptor activation, and loss-of-function mutations resulting in non-functional or dominant negative receptors, have been observed.
In the present study, we have analyzed the mutations of receptor families (patched ; a receptor for the hedgehog protein, fibroblast growth factor receptor (FGFR)-1, -2, -3, Tie-2 ; an endothelial cell-specific receptor tyrosine kinase) that are involved in inherited syndromes (nevoid basal cell carcinoma syndrome ; NBCCS/Gorlin Syndrome, craniosynostosis, achondroplasia, oral cancers and venous malformations, respectively) by both PCR-SSCP and direct sequencing of the DNA derived from peripheral blood lymphocytes and saliva, to examine the phenotype/genotype correlations in patients with the syndromes. In addition, we have studied cellular growth, differentiation and intracellular signal transduction pathways in the target cells expressing mutated genes to elucidate the molecular function of the mutated receptor genes in the syndromes.
We describes the molecular consequences of the disease mutations, and predicts that many novel mutations remain to be identified.
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