title: Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses.
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 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.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U 393, Institut Necker and Assistance publique, Hôpitaux de Paris, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Delezoide
authors.forename: C
authors.initials: C
authors.lastname: Lasselin-Benoist
authors.forename: L
authors.initials: L
authors.lastname: Legeai-Mallet
authors.forename: P
authors.initials: P
authors.lastname: Brice
authors.forename: V
authors.initials: V
authors.lastname: Senée
authors.forename: A
authors.initials: A
authors.lastname: Yayon
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: J
authors.initials: J
authors.lastname: Bonaventure
mesh_terms: D002356:Cartilage / Q000196:embryology / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005315:Fetal Diseases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006132:Growth Plate / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D013796:Thanatophoric Dysplasia / Q000196:embryology / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3