Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression - Archive ouverte HAL Access content directly
Journal Articles Developmental Dynamics Year : 1994

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.
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hal-03991580 , version 1 (15-02-2023)

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Filippo M. Rijli, Pascal Dollé, Valerie Fraulob, Marianne Lemeur, Pierre Chambon. Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression. Developmental Dynamics, 1994, 201 (4), pp.366-377. ⟨10.1002/aja.1002010408⟩. ⟨hal-03991580⟩
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