Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome.
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.
Schwabe
Georg C
GC
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Trepczik
Britta
B
Süring
Kathrin
K
Brieske
Norbert
N
Tucker
Abigail S
AS
Sharpe
Paul T
PT
Minami
Yasuhiro
Y
Mundlos
Stefan
S
D000818:Animals; D025063:Chromosome Disorders / Q000196:embryology / Q000473:pathology; D002874:Chromosome Mapping; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000166:cytology; D017353:Gene Deletion; D005835:Genitalia / Q000473:pathology; D005838:Genotype; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D019170:Somites / Q000473:pathology; D013577:Syndrome
D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse