A mouse model for human short-stature syndromes identifies Shox2 as an upstream regulator of Runx2 during long-bone development.

  • publication
  • 16-03-2006

Cobb J, Dierich A, Huss-Garcia Y, Duboule D. Proc. Natl. Acad. Sci. U.S.A. 2006 Mar;103(12):4511-5. 0510544103. 10.1073/pnas.0510544103. PMC1450202.

Deficiencies or mutations in the human pseudoautosomal SHOX gene are associated with a series of short-stature conditions, including Turner syndrome, Leri-Weill dyschondrosteosis, and Langer mesomelic dysplasia. Although this gene is absent from the mouse genome, the closely related paralogous gene Shox2 displays a similar expression pattern in developing limbs. Here, we report that the conditional inactivation of Shox2 in developing appendages leads to a strong phenotype, similar to the human conditions, although it affects a different proximodistal limb segment. Furthermore, using this mouse model, we establish the cellular etiology of these defects and show that Shox2 acts upstream the Runx2 gene, a key regulator of chondrogenesis.

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