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Publication : Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression.

First Author  Rijli FM Year  1994
Journal  Dev Dyn Volume  201
Issue  4 Pages  366-77
PubMed ID  7894075 Mgi Jnum  J:21946
Mgi Id  MGI:69846 Doi  10.1002/aja.1002010408
Citation  Rijli FM, et al. (1994) Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression. Dev Dyn 201(4):366-77
abstractText  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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