Abnormal FGFR 3 Expression in Cartilage of Thanatophoric Dysplasia Fetuses

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 w...

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Bibliographic Details
Published in:Human molecular genetics 1997-10, Vol.6 (11), p.1899-1906
Main Authors: Delezoide, Anne-Lise, Lasselin-Benoist, Catherine, Legeai-Mallet, Laurence, Brice, Peggy, Senée, Valérie, Yayon, Avner, Munnich, Arnold, Vekemans, Michel, Bonaventure, Jacky
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cartilage - embryology
Cartilage - metabolism
Chondrocytes - metabolism
Diseases of the osteoarticular system
Embryonic and Fetal Development
Fetal Diseases - metabolism
Fluorescent Antibody Technique
Gene Expression
Growth Plate - metabolism
Humans
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical sciences
Mutation
Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 3
Receptors, Fibroblast Growth Factor - biosynthesis
Receptors, Fibroblast Growth Factor - genetics
RNA, Messenger - metabolism
Thanatophoric Dysplasia - embryology
Thanatophoric Dysplasia - metabolism
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Summary: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.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/6.11.1899