Synpolydactyly in mice with a targeted deficiency in the HoxD complex.
The morphogenesis of mammalian digits requires the function of several genes of the HoxD complex during development of limb buds. Using embryonic stem (ES) cells and a site-specific recombination system (loxP/Cre), we have induced a deficiency 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 synpolydactyly, 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.
Department of Zoology and Animal Biology, University of Geneva, Sciences III, Switzerland.
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Zákány
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Duboule
D000818:Animals; D017353:Gene Deletion; D018390:Gene Targeting; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D017689:Polydactyly / Q000235:genetics*; D013234:Stem Cells; D013576:Syndactyly / Q000235:genetics*; D013577:Syndrome; D014034:Toes / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics
D018398:Homeodomain Proteins; C490939:Hoxd11 protein, mouse; D014157:Transcription Factors