Abnormal FGFR 3 Expression in Cartilage of Thanatophoric Dysplasia Fetuses
Open Access
- 1 October 1997
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 6 (11) , 1899-1906
- https://doi.org/10.1093/hmg/6.11.1899
Abstract
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 chondro-cytes. 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 chon-drocyte differentiation.Keywords
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