Beckers J, Duboule D
Department of Zoology and Animal Biology, Sciences III, University of Geneva, Switzerland.
Dev Dyn. 1998 Sep;213(1):1-11. doi: 10.1002/(SICI)1097-0177(199809)213:1<1::AID-AJA1>3.0.CO;2-L.
Extensive sequencing in the HoxD complex of several vertebrate species has revealed a set of conserved DNA sequences interspersed between neighboring Hox genes. Their high degree of conservation strongly suggested that they are used for regulatory purposes, a hypothesis that was largely confirmed by using "classical transgenesis" or in vivo mutagenesis through the embryonic stem (ES) cell technology. Here, we show that this is not always the case. We report that the deletion of a conserved regulatory sequence located in the HoxD complex gives different results, depending on the transgenic approach that was used. In "conventional" transgenesis, this sequence was necessary for proper expression in a subdomain of the developing limb. However, a deletion of this sequence in complexo did not confirm this effect, thereby creating an important discrepancy between the classical transgenic and the ES cell-based, targeted mutagenesis. This unexpected observation may show the limitations of the former technology. Alternatively, it could illustrate a redundancy in regulatory circuits and, thus, justify the combination of parallel strategies.
对几种脊椎动物物种的HoxD复合体进行的广泛测序揭示了一组散布在相邻Hox基因之间的保守DNA序列。它们高度的保守性强烈表明它们用于调控目的，这一假设在很大程度上通过使用“经典转基因技术”或通过胚胎干细胞（ES细胞）技术进行体内诱变得到了证实。在这里，我们表明情况并非总是如此。我们报告说，位于HoxD复合体中的一个保守调控序列的缺失会产生不同的结果，这取决于所使用的转基因方法。在“传统”转基因中，该序列对于在发育中的肢体的一个子域中正确表达是必需的。然而，在复合体中删除该序列并未证实这种效应，从而在经典转基因和基于ES细胞的靶向诱变之间产生了重要差异。这一意外发现可能表明了前一种技术的局限性。或者，它可以说明调控回路中的冗余，因此证明并行策略组合的合理性。
