Fibroblast Growth Factor Receptor 3 Mutations in Achondroplasia and Related Forms of Dwarfism

@article{Horton2004FibroblastGF,
  title={Fibroblast Growth Factor Receptor 3 Mutations in Achondroplasia and Related Forms of Dwarfism},
  author={William A. Horton and Gregory P. Lunstrum},
  journal={Reviews in Endocrine and Metabolic Disorders},
  year={2004},
  volume={3},
  pages={381-385}
}
  • W. Horton, G. Lunstrum
  • Published 1 December 2002
  • Medicine, Biology
  • Reviews in Endocrine and Metabolic Disorders
Abbreviations: ACH, achondroplasia; BMP, bone morphogenetic protein; ERK, extracellular signal-related protein kinase; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; HYP, hypochondroplasia; MAPK, mitogen activated protein kinase; PI3K, phosphoinositol phosphate-3-kinase; PLCγ , phospholipase C gamma; SH2, src homology 2; Sox, sry-like high mobility group box transcription factor; STAT, signal transducer and activator of transcription; TD, thanatophoric dysplasia. 
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References

SHOWING 1-10 OF 46 REFERENCES
Fibroblast growth factor receptor 3 and the human chondrodysplasias.
  • W. Horton
  • Medicine, Biology
    Current opinion in pediatrics
  • 1997
TLDR
Heterozygous mutations of the gene encoding the fibroblast growth factor receptor 3 (FGFR3) have been found in persons with achondroplasia, thanatophoric dysplasia; specific mutations strongly correlate with the clinical severity of disease.
Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia.
TLDR
The results suggest that the molecular basis of achondroplasia is unregulated signal transduction through FGFR3, which may result in inappropriate cartilage growth plate differentiation and thus abnormal long bone development.
Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia
TLDR
It is shown that each of the mutations constitutively activate the receptor, as evidenced by ligand-independent receptor tyro-sine phosphorylation and cell proliferation, providing a biochemical explanation for the observation that the phenotype of TD is more severe than that of ACH.
Activation of Statl by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism
TLDR
It is shown that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Statl, which may be used as a mediator of growth retardation in bone development in achondroplasia class of chondrodysplasias.
Fibroblast Growth Factor Receptor 3 Mutations Promote Apoptosis but Do Not Alter Chondrocyte Proliferation in Thanatophoric Dysplasia*
TLDR
Results indicate that FGFR 3 mutations in TD I fetuses do not hamper chondrocyte proliferation but rather alter their differentiation by triggering premature apoptosis through activation of the STAT signaling pathway.
A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3.
  • Y. Wang, M. Spatz, D. Givol
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
These experiments demonstrate that achondroplasia results from a gain-of-FGFR3-function leading to inhibition of chondrocyte proliferation and represents a reliable and useful model for developing drugs for potential treatment of the human disease.
Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia
TLDR
It appears that recurrent mutations of a single amino acid in the transmembrane domain of the FGFR3 protein account for all cases of achondroplasia in the series of sporadic cases reported.
Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3
TLDR
It is demonstrated that Fgfr3 is essential for normal endochondral ossification and inner ear development and Contrasts between the skeletal phenotype and achondroplasia suggest that activation of FGFR3 causes achondaplasia.
Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.
TLDR
An essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification is revealed, which is correlated with the activation of Stat proteins and upregulation of cell-cycle inhibitors.
...
1
2
3
4
5
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