GENETIC-ANALYSIS OF A CONSERVED SEQUENCE IN THE HOXD COMPLEX - REGULATORY REDUNDANCY OR LIMITATIONS OF THE TRANSGENIC APPROACH

Extensive sequencing in the HoxD complex of several vertebrate species has revealed a set of conserved DNA sequences interspersed between ne ighboring Hox genes. Their high degree of conservation strongly sugges ted that they are used for regulatory purposes, a hypothesis that was largely confirmed by using ''classical transgenesis'' or in vivo mutag enesis through the embryonic stem (ES) cell technology. Here, we show that this is not always the case. We report that the deletion of a con served regulatory sequence located in the HoxD complex gives different results, depending on the transgenic approach that was used. In ''con ventional'' transgenesis, this sequence was necessary for proper expre ssion in a subdomain of the developing limb. However, a deletion of th is sequence in complexo did not confirm this effect, thereby creating an important discrepancy between the classical transgenic and the ES c ell-based, targeted mutagenesis, This unexpected observation may show the limitations of the former technology. Alternatively, it could illu strate a redundancy in regulatory circuits and, thus, justify the comb ination of parallel strategies. Dev. Dyn. 1998;213:1-11. (C) 1998 Wile y-Liss, Inc.