Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

Dev Dyn. 2004 Feb;229(2):400-10. doi: 10.1002/dvdy.10466.


Robinow syndrome (RS) is a human dwarfism syndrome characterized by mesomelic limb shortening, vertebral and craniofacial malformations and small external genitals. We have analyzed Ror2(-/-) mice as a model for the developmental pathology of RS. Our results demonstrate that vertebral malformations in Ror2(-/-) mice are due to reductions in the presomitic mesoderm and defects in somitogenesis. Mesomelic limb shortening in Ror2(-/-) mice is a consequence of perturbed chondrocyte differentiation. Moreover, we show that the craniofacial phenotype is caused by a midline outgrowth defect. Ror2 expression in the genital tubercle and its reduced size in Ror2(-/-) mice makes it likely that Ror2 is involved in genital development. In conclusion, our findings suggest that Ror2 is essential at multiple sites during development. The Ror2(-/-) mouse provides a suitable model that may help to explain many of the underlying developmental malformations in individuals with Robinow syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Disorders / embryology
  • Chromosome Disorders / pathology
  • Chromosome Mapping
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / pathology
  • Disease Models, Animal*
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / cytology
  • Gene Deletion
  • Genitalia / pathology
  • Genotype
  • Humans
  • Limb Deformities, Congenital / genetics
  • Limb Deformities, Congenital / pathology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Somites / pathology
  • Syndrome


  • Receptor Protein-Tyrosine Kinases
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Ror2 protein, mouse