Targeted disruption in the mouse HoxC-4 locus results in axial skeleton homeosis and malformation of the xiphoid process

Abstract

Hoxc-4 is a mouse homeobox gene located at the 3' end of the HoxC cluster. Of the HoxC genes, Hoxc-4 is expressed in the most anterior regions of the central nervous system and prevertebral column. To investigate its role in mouse development, we have generated Hoxc-4 mutant mice by gene targeting. Mice homozygous for the Hoxc-4 mutation are viable and fertile. Analysis of the skeletal system of homozygous mutants revealed various abnormalities in the cervical and thoracic regions. The most frequent abnormality was a partial posterior homeotic transformation of the seventh cervical vertebra. Less frequently, anterior transformations of the third and eighth thoracic vertebrae were observed. furthermore, the xiphoid process of the sternum was malformed such that it had an aperture or a fissure. Although Hoxc-4 is expressed abundantly in the central nervous system, no obvious defects were observed. These results suggest that Hoxc-4 is required for specifying cervical and thoracic vertebral identity.