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Molecularbiological study of craniofacial dysmorphology in transgenic mice bearing Apert type mutant Fgfr2 gene

Research Project

Project/Area Number 14571883
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

NAGATA Masaki  NIIGATA UNIVERSITY, Graduate school of medical and dental sciences, Assistant, 大学院・医歯学総合研究科, 助手 (10242439)

Co-Investigator(Kenkyū-buntansha) AMIZUKA Norio  NIIGATA UNIVERSITY, Graduate school of medical and dental sciences, Associate professor, 大学院・医歯学総合研究科, 助教授 (30242431)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsApert syndrome / Fgfr2 / chondrocyte differentiation / Cranial base / Transgenic mouse / 頭蓋形態形成 / 頭蓋発生 / 頭蓋縫合
Research Abstract

To test a hypothesis that the cartilage is another target for the mutant FGFR2 signaling, we generated transgenic mice expressing Fgfr2 IIIc bearing Apert syndrome type mutation (Fgfr2 IIIc^<P253R>) selectively in chondrocytes. These mice markedly manifested deformities of the cranium including premature fusion of cartilaginous sutures in the cranial base(synchondroses), which accompanied by domed skull with wide opened metopic suture, maxillary hypoplasia, and shortening of anterior cranial base. As a likely cause of the prominent cranial deformities, we hypothesized specific expression patterns of FGF ligands that could produce aberrant FGFR2 signaling in cranial cartilage. The results of gene expression analyses by Lasermicrodisection(LMD)/Real time PCR(R-PCR) and organ culture system with FGFs stimulation demonstrated the acquirement of edopic autocrine regulation by Fgfi2 IIIc^<P253R> expression in concert with the specific distribution pattern of FGF2 and FGF10 ligand in cranial base cartilage. These results propose importance role of abnormal development of the cranial base cartilage as another basic mechanism of the preferential craniofacial dysmorphologies in Apert syndrome. To clarify the biological effect of activation of FGFR2 signaling, we used the LMD/R-PCR system to analyze the differentiation markers for chondrocyte lineage cells. Consistent with histological findings, LMD/R-PCR data have suggested activation of the molecules, Cbfa1, Ihh and MMP-13,which are involved in hypertrophic differentiation of the chondrocyte. Taken together, aberrant activation of FGFR2 signaling in cranial cartilage could result acceleration of chondrocyte terminal differentiation, consequently, resulting the craniofacial dysmorphology with premature fusion of cranial synchondroses.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Amizuka, N., Seki, Y., Maeda, T.: "Ultrastructural findings on bone metastasis of tumor cells. 12(6) : 2002"Clinical Calcium. 12. 137-145 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤田 一, 永田昌毅, 小野和宏, 高木律男: "日本人唇裂・唇顎口蓋裂患者における19q13.2領域のマイクロサテライト多型を用いた連鎖解析"口腔科学会誌. 51(1). 15-22 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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