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对四足动物和鱼类中存在的一种潜在Hoxd-11肢体调控元件的转基因分析。

Transgenic analysis of a potential Hoxd-11 limb regulatory element present in tetrapods and fish.

作者信息

Beckers J, Gérard M, Duboule D

机构信息

Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, Geneva 4, 1211, Switzerland.

出版信息

Dev Biol. 1996 Dec 15;180(2):543-53. doi: 10.1006/dbio.1996.0327.

DOI:10.1006/dbio.1996.0327
PMID:8954726
Abstract

Genes of the HoxD complex related to the Drosophila Abd-B gene are involved in the morphogenesis of vertebrate paired appendages. Hoxd-11, for instance, is necessary in combination with other Hox genes for the proper development of different parts of the tetrapod limbs. Sequence comparisons between the mouse, chicken, and zebrafish Hoxd-11 loci have revealed the conservation of several blocks of DNA sequence which may be of importance for the regulation of Hoxd-11 expression. We have used transgenic mice to show that one of these conserved elements specifically drives expression in a proximal-posterior part of developing forelimbs. Production of mice transgenic for a full fish Hoxd-11 construct as well as for mouse-fish Hoxd-11 chimeric constructs shows that the fish counterpart of this sequence is able to elicit expression in mouse forelimbs as well, though in a slightly different domain. However, this fish element requires the presence of the mouse promoter and does not work in its own context. These results are discussed in light of both the control of Hoxd gene expression during limb development and the use of a comparative interspecies approach to understand the regulation of genes involved in vertebrate development.

摘要

与果蝇Abd - B基因相关的HoxD复合体基因参与脊椎动物成对附肢的形态发生。例如,Hoxd - 11与其他Hox基因共同作用,对四足动物肢体不同部位的正常发育是必需的。对小鼠、鸡和斑马鱼Hoxd - 11基因座的序列比较揭示了几个DNA序列块的保守性,这些序列块可能对Hoxd - 11表达的调控很重要。我们利用转基因小鼠表明,这些保守元件之一特异性地驱动发育中前肢近端后部的表达。对完整鱼类Hoxd - 11构建体以及小鼠 - 鱼类Hoxd - 11嵌合构建体进行转基因小鼠的制备,结果表明该序列的鱼类对应物也能够在小鼠前肢中引发表达,尽管表达区域略有不同。然而,这个鱼类元件需要小鼠启动子的存在,在其自身环境中不起作用。结合肢体发育过程中Hoxd基因表达的控制以及使用种间比较方法来理解脊椎动物发育相关基因的调控,对这些结果进行了讨论。

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