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Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions

Nature volume 370, pages 304–307 (1994)Cite this article

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.

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  1. Mario R. Capecchi: To whom correspondence should be addressed.

Authors and Affiliations

  1. 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

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  1. Brian G. Condie
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  2. Mario R. Capecchi
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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

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