Schwabe Georg C, Trepczik Britta, Süring Kathrin, Brieske Norbert, Tucker Abigail S, Sharpe Paul T, Minami Yasuhiro, Mundlos Stefan
Max Planck Institute for Molecular Genetics, Berlin, Germany.
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.
罗宾诺综合征（RS）是一种人类侏儒症综合征，其特征为中肢短小、脊柱和颅面畸形以及外生殖器小。我们分析了Ror2基因敲除小鼠作为RS发育病理学的模型。我们的结果表明，Ror2基因敲除小鼠的脊柱畸形是由于体节中胚层减少和体节发生缺陷所致。Ror2基因敲除小鼠的中肢短小是软骨细胞分化受干扰的结果。此外，我们表明颅面表型是由中线生长缺陷引起的。Ror2在生殖结节中的表达及其在Ror2基因敲除小鼠中的尺寸减小表明Ror2可能参与生殖发育。总之，我们的研究结果表明Ror2在发育过程中的多个部位至关重要。Ror2基因敲除小鼠提供了一个合适的模型，可能有助于解释罗宾诺综合征患者许多潜在的发育畸形。
