title: Genetic analysis of a conserved sequence in the HoxD complex: regulatory redundancy or limitations of the transgenic approach?
abstract: 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.
authors.affiliation: Department of Zoology and Animal Biology, Sciences III, University of Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Beckers
authors.forename: D
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000483:Alleles; D000818:Animals; D017124:Conserved Sequence; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*; D014566:Urogenital System / Q000196:embryology
chemical_list: D018398:Homeodomain Proteins; C490939:Hoxd11 protein, mouse; C490943:Hoxd12 protein, mouse; D014157:Transcription Factors