Human Molecular Genetics, Vol 6, 1899-1906, Copyright © 1997 by Oxford University Press
AL Delezoide, C Lasselin-Benoist, L Legeai-Mallet, P Brice, V Senee, A Yayon, A Munnich, M Vekemans and J Bonaventure
Thanatophoric dysplasia (TD), the commonest lethal skeletal dysplasia in
humans, is accounted for by recurrent mutations in the fibroblast growth
factor receptor 3 gene (FGFR 3), causing its constitutive activation in
vitro. Taking advantage of medical abortion of 18 TD fetuses, cartilage
sections were studied for FGFR 3 gene expression by in situ hybridization
and immunohistochemistry. Specific antibodies revealed high amounts of FGFR
3 in cartilage of TD fetuses with no increased level of the corresponding
mRNA. The specific signal was mainly detected in the nucleus of
proliferative and hypertrophic chondrocytes. Based on this observation and
the abnormal expression of collagen type X in hypertrophic TD chondrocytes,
we suggest that constitutive activation of the receptor through formation
of a stable dimer increases its stability and promotes its translocation
into the nucleus, where it might interfere with terminal chondrocyte
differentiation.
ARTICLES
Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses
Unite de Recherches sur les Handicaps Genetiques de l'Enfant, INSERM U 393, Institut Necker and Assistance publique, Hopitaux de Paris, France.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Y. Cho, C. Guo, M. Torello, G. P. Lunstrum, T. Iwata, C. Deng, and W. A. Horton Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia PNAS, January 13, 2004; 101(2): 609 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cormier, A.-L. Delezoide, C. Benoist-Lasselin, L. Legeai-Mallet, J. Bonaventure, and C. Silve Parathyroid Hormone Receptor Type 1/Indian Hedgehog Expression Is Preserved in the Growth Plate of Human Fetuses Affected with Fibroblast Growth Factor Receptor Type 3 Activating Mutations Am. J. Pathol., October 1, 2002; 161(4): 1325 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwata, C.-L. Li, C.-X. Deng, and C. A. Francomano Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice Hum. Mol. Genet., June 1, 2001; 10(12): 1255 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Wysolmerski, S. Cormier, W. M. Philbrick, P. Dann, J.-P. Zhang, J. Roume, A.-L. Delezoide, and C. Silve Absence of Functional Type 1 Parathyroid Hormone (PTH)/PTH-Related Protein Receptors in Humans Is Associated with Abnormal Breast Development and Tooth Impaction J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1788 - 1794. [Abstract] [Full Text]
|
|
|
|
|
|
O. Segev, I. Chumakov, Z. Nevo, D. Givol, L. Madar-Shapiro, Y. Sheinin, M. Weinreb, and A. Yayon Restrained chondrocyte proliferation and maturation with abnormal growth plate vascularization and ossification in human FGFR-3G380R transgenic mice Hum. Mol. Genet., January 22, 2000; 9(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Monsonego-Ornan, R. Adar, T. Feferman, O. Segev, and A. Yayon The Transmembrane Mutation G380R in Fibroblast Growth Factor Receptor 3 Uncouples Ligand-Mediated Receptor Activation from Down-Regulation Mol. Cell. Biol., January 15, 2000; 20(2): 516 - 522. [Abstract] [Full Text]
|
|
|
|
|
|
D. Grisaru, E. Lev-Lehman, M. Shapira, E. Chaikin, J. B. Lessing, A. Eldor, F. Eckstein, and H. Soreq Human Osteogenesis Involves Differentiation-Dependent Increases in the Morphogenically Active 3' Alternative Splicing Variant of Acetylcholinesterase Mol. Cell. Biol., January 1, 1999; 19(1): 788 - 795. [Abstract] [Full Text] [PDF]
|
|