Abnormal FGFR 3 Expression in Cartilage of Thanatophoric Dysplasia Fetuses

• 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
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/6.11.1899

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.