Insertion of a targeting construct in a Hoxd‐10 allele can influence the control of Hoxd‐9 expression

Abstract

A neomycin resistance (neo) gene driven by the phosphoglycerokinase (PGK) promoter was inserted into the Hoxd‐10 homeobox by homologous recombination in embryonic stem (ES) cells. Chimeric mice derived from ES cell‐injected blastocysts died shortly after birth. Craniofacial and axial abnormalities were found in the skeleton of these chimeras, resembling some of the previously described Hox gene gain‐of‐function phenotypes. The spatial expression patterns of various Hoxd gene transcripts were analysed in chimeric mutant embryos by in situ hybridization. Two main observations were made: (1) a wide ectopic expression domain of the Hoxd‐9 gene was found in the spinal cord of these embryos, and (2) the neo gene exhibited a specific Hox‐like expression domain which extended far more rostrally than that of the Hoxd‐10 gene, showing that, in the context of this mutation, the PGK promoter could be regulated as a Hox promoter. These results provide the first evidence that a targeted insertion into a Hox gene coding sequence, in the context of its own cluster, could result in misexpression of a neighbour gene of the complex. © 1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss, Inc.