Abstract
THE morphogenesis of mammalian digits requires the function of several genes of the HoxD complex during development of limb buds1–4. Using embryonic stem (ES) cells and a site-specific recombination system (loxP/Cre), we have induced a deficiency5,6 that eliminates the products of the Hoxd-13, Hoxd-12 and Hoxd-11 genes simultaneously. A Hoxd-11/lacz reporter gene replaced the deleted region in order to monitor the effect of this triple inactivation at the cellular level. Mice homozygous for this deficiency showed small digit primordia, a disorganized cartilage pattern and impaired skeletal mass. These alterations are similar to the defects seen in a human synpolydactyly7,8, suggesting that this syndrome, which is associated with a subtle mutation in HOXD13 (ref. 8), may involve the loss of function of several Hoxd genes. These results indicate the existence of a functional hierarchy among these genes and provide us with an animal model to study human digit malformations.
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Zákány, J., Duboule, D. Synpolydactyly in mice with a targeted deficiency in the HoxD complex. Nature 384, 69–71 (1996). https://doi.org/10.1038/384069a0
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DOI: https://doi.org/10.1038/384069a0
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