Synpolydactyly in mice with a targeted deficiency in the HoxD complex
Synpolydactyly in mice with a targeted deficiency in the HoxD complex
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DOI：
10.1038/384069a0
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发表时间：
1996-11-07
期刊：
影响因子：
64.8
通讯作者：
Duboule, D
中科院分区：
文献类型：
--
作者：
Zakany, J;Duboule, D
哺乳动物手指的形态发生需要在肢芽发育过程中HoxD复合体的几个基因的功能(1-4)。利用胚胎干细胞和位点特异性重组系统(loxP/Cre)，我们诱导了一个缺陷(5，6)，它同时消除了Hoxd-13，Hoxd-12和Hoxd-11基因的产物。Hoxd-11/LacZ报告基因取代了缺失的区域，以便在细胞水平上监测这种三重失活的影响。这一缺陷的纯合子小鼠表现为小指原基、杂乱无章的软骨图案和受损的骨骼质量。这些改变类似于人类并指症(7，8)的缺陷，表明这种综合征与Hoxd13的一个细微突变有关。8)，可能涉及几个牛群基因功能的丧失。这些结果表明这些基因之间存在一个功能层次结构，并为我们提供了一个研究人类手指畸形的动物模型。
THE morphogenesis of mammalian digits requires the function of several genes of the HoxD complex during development of limb buds(1-4). Using embryonic stem (ES) cells and a site-specific recombination system (loxP/Cre), we have induced a deficiency(5,6) 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 synpolydactyly(7,8), suggesting that this syndrome, which is associated with a subtle mutation in HOXD13 (ref. 8), may involve the loss of function of several Herd 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.