title: Cloning and expression pattern of chicken Ror2 and functional characterization of truncating mutations in Brachydactyly type B and Robinow syndrome.
abstract: Ror2 is a receptor tyrosine kinase mutated in the human syndromes Brachydactyly type B (BDB) and recessive Robinow syndrome (RS). In this study, we used the chick as a model to investigate the role of Ror2 in skeletogenesis and to elucidate the functional consequences of Ror2 mutations. For this purpose, we cloned chicken Ror2 and analyzed its expression pattern at various embryonic stages by in situ hybridization and immunolabeling. We document expression of cRor2 in several organs, including mesonephros, heart, nervous system, intestine and cartilage. The high conservation of expression when compared with the mouse underlines the validity of the chick as a model system. Using replication-competent retroviral vector-mediated overexpression, we analyzed the functional consequences of truncating BDB and RS mutations in the developing chick limb. Overexpression of Ror2 mutants led to a disturbance of growth plate architecture and a severe block of chondrocyte differentiation, demonstrating the functional importance of Ror2 in skeletogenesis.
authors.affiliation: Max Planck-Institute for Molecular Genetics, Development and Disease Group, Berlin, Germany. strick_s@molgen.mpg.de
authors.forename: Sigmar
authors.initials: S
authors.lastname: Stricker
authors.forename: Nicole
authors.initials: N
authors.lastname: Verhey van Wijk
authors.forename: Florian
authors.initials: F
authors.lastname: Witte
authors.forename: Norbert
authors.initials: N
authors.lastname: Brieske
authors.forename: Kathrin
authors.initials: K
authors.lastname: Seidel
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology; D003001:Cloning, Molecular; D015342:DNA Probes / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D017880:Limb Deformities, Congenital / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D029742:Caenorhabditis elegans Proteins; D015342:DNA Probes; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors