Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Development / genetics
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Bone and Bones / abnormalities
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Chondrocytes / chemistry
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Chondrocytes / metabolism
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Chondrogenesis / genetics*
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Core Binding Factor Alpha 1 Subunit / analysis
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Core Binding Factor Alpha 1 Subunit / genetics*
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Disease Models, Animal*
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Gene Expression Regulation, Developmental*
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Growth Disorders / genetics*
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Growth Disorders / pathology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Limb Deformities, Congenital / genetics
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Limb Deformities, Congenital / pathology
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Mice / genetics*
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Mice, Mutant Strains
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Phenotype
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Sequence Deletion
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Syndrome
Substances
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Core Binding Factor Alpha 1 Subunit
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Homeodomain Proteins
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Runx2 protein, mouse
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Shox2 protein, mouse