Alternative titles; symbols
HGNC Approved Gene Symbol: HOXA3
Cytogenetic location: 7p15.2 Genomic coordinates (GRCh38): 7:27,107,010-27,152,583 (from NCBI)
To examine directly the nature of functional overlap within the Hox3 group, Greer et al. (2000) exchanged reciprocally in the genome of mice the protein-coding portions of the Hoxa3 and Hoxd3 (142980) genes. Thus, they generated mice that lacked any Hoxa3 protein but instead expressed the Hoxd3 protein from both the Hoxa3 and Hoxd3 loci, as well as mice that lacked Hoxd3 protein but expressed Hoxa3 from both loci. Embryos representing all Hoxa3 allelic combinations were examined histologically. At embryonic day 17.5, homozygous null Hoxa3 embryos demonstrated complete absence of the thymus. However, replacement of one or both copies of the Hoxa3 protein with the Hoxd3 protein restored this organ. Alterations of the hyoid cartilage, which is characteristic of embryos homozygous for the null allele of Hoxa3, were reversed by expression of the Hoxd3 protein at the Hoxa3 locus. One conclusion from these data was that the Hoxd3 protein is functionally equivalent to the Hoxa3 protein if it is expressed in the context of the Hoxa3 gene. A corollary would be that the Hoxa3 protein, if expressed at the Hoxd3 locus, would be unable to complement null mutations at Hoxa3. This was shown to be the case. Hoxa3 protein was able to complement Hoxd3 deficiency when expressed in the context of the Hoxd3 allele. Greer et al. (2000) concluded that bidirectional complementation demonstrated that these proteins, which share less than 50% identity in the amino acid sequence, are capable of carrying out equivalent biologic functions in the processes recognized to require Hox3 gene activity. In addition, it provided direct evidence that the different roles played by these genes during embryogenesis are mainly the result of cis-acting sequences that modulate expression of the individual loci.
Greer, J. M., Puetz, J., Thomas, K. R., Capecchi, M. R. Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403: 661-665, 2000. [PubMed: 10688203] [Full Text: https://doi.org/10.1038/35001077]