Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions (original) (raw)
- Letter
- Published: 28 July 1994
Nature volume 370, pages 304–307 (1994)Cite this article
- 873 Accesses
- 227 Citations
- Metrics details
An Erratum to this article was published on 06 October 1994
Abstract
THE Hox genes encode transcription factors which mediate the formation of the mammalian body plan along the anteroposterior and appendicular axes1–15. Paralogous Hox genes within the separate linkage groups are closely related with respect to DNA sequence and expression16,17, suggesting that they could have at least partially redundant functions. We showed previously that mice homozygous for independent targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 had no defects in common1,8. But our current analysis of double mutants has revealed strong, dosage-dependent interactions between these genes. We report here that in _hoxd-3_- homozygotes the first cervical vertebra, the atlas, is homeotically transformed to the adjacent anterior structure. Unexpectedly, in double mutants, rather than observing a more extensive homeotic transformation, the entire atlas is deleted. These observations are interpreted in terms of a model in which these Hox genes differentially regulate the proliferation rates of the appropriate sets of precursor cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Similar content being viewed by others
References
- Chisaka, O. & Capecchi, M. R. Nature 350, 473–479 (1991).
Article ADS CAS Google Scholar - Lufkin, T., Dierich, A., LeMeur, M., Mark, M. & Chambon, P. Cell 66, 1105–1119 (1991).
Article CAS Google Scholar - Chisaka, O., Musci, T. S. & Capecchi, M. Nature 355, 516–520 (1992).
Article ADS CAS Google Scholar - LeMouellic, H., Lallemand, Y. & Brûlet, P. Cell 69, 251–264 (1992).
Article CAS Google Scholar - Ramirez-Solis, R., Zheng, H., Whiting, J., Krumlauf, R. & Bradley, A. Cell 73, 279–294 (1993).
Article CAS Google Scholar - Carpenter, E. M., Goddard, J. M., Chiska, O., Manley, N. R. & Capecchi, M. R. Development 118, 1063–1075 (1993).
CAS PubMed Google Scholar - Mark, M. et al. Development 119, 319–338 (1993).
CAS PubMed Google Scholar - Condie, B. G. & Capecchi, M. R. Development 119, 579–595 (1993).
CAS Google Scholar - Jeannotte, L., Lemieux, M., Charron, J., Poirier, F. & Robertson, E. J. Genes Dev. 7, 2085–2096 (1993).
Article CAS Google Scholar - Dollé, P. et al. Cell 75, 431–441 (1993).
Article Google Scholar - Small, K. M. & Potter, S. S. Genes Dev. 7, 2318–2328 (1993).
Article CAS Google Scholar - Gendron-Maguire, M., Mallo, M., Zhang, M. & Gridley, T. Cell 75, 1317–1331 (1993).
Article CAS Google Scholar - Rijli, F. M. et al. Cell 75, 1333–1349 (1993).
Article CAS Google Scholar - Kostic, D. & Capecchi, M. R. Mech. Dev. (in the press).
- Davis, A. P. & Capecchi, M. R. Development (in the press).
- Hunt, P. et al. Nature 353, 861–864 (1991).
Article ADS CAS Google Scholar - McGinnis, W. & Krumlauf, R. Cell 68, 283–302 (1992).
Article CAS Google Scholar - Aberdam, D., Negreanu, V., Sachs, L. & Blatt, C. Molec. cell. Biol. 11, 554–557 (1991).
Article CAS Google Scholar - Dollé, P. et al. Proc. natn. Acad. Sci. U.S.A. 90, 7666–7670 (1993).
Article ADS Google Scholar - Kessel, M. & Gruss, P. Cell 67, 89–104 (1991).
Article CAS Google Scholar - Mansour, S. L., Goddard, J. M. & Capecchi, M. R. Development 117, 13–28 (1993).
CAS Google Scholar - Jegalian, B. G. & DeRobertis, E. M. Cell 71, 901–910 (1992).
Article CAS Google Scholar
Author information
Author notes
- Mario R. Capecchi: To whom correspondence should be addressed.
Authors and Affiliations
- Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, 84112, USA
Brian G. Condie & Mario R. Capecchi
Authors
- Brian G. Condie
You can also search for this author inPubMed Google Scholar - Mario R. Capecchi
You can also search for this author inPubMed Google Scholar
Rights and permissions
About this article
Cite this article
Condie, B., Capecchi, M. Mice with targeted disruptions in the paralogous genes _hoxa_-3 and _hoxd_-3 reveal synergistic interactions.Nature 370, 304–307 (1994). https://doi.org/10.1038/370304a0
- Received: 18 April 1994
- Accepted: 24 June 1994
- Issue Date: 28 July 1994
- DOI: https://doi.org/10.1038/370304a0