TARGETED DISRUPTION IN THE MOUSE HOXC-4 LOCUS RESULTS IN AXIAL SKELETON HOMEOSIS AND MALFORMATION OF THE XIPHOID PROCESS

Hoxc-4 is a mouse homeobox gene located at the 3' end of the HoxC clus ter. Of the HoxC genes, Hoxc-4 is expressed in the most anterior regio ns of the central nervous system and prevertebral column. To investiga te 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 re vealed various abnormalities in the cervical and thoracic regions. The most frequent abnormality was a partial posterior homeotic transforma tion of the seventh cervical vertebra. Less frequently, anterior trans formations of the third and eighth thoracic vertebrae were observed. F urthermore, the xiphoid process of the sternum was malformed such that it had an aperture or a fissure. Although Hoxc-4 is expressed abundan tly in the central nervous system, no obvious defects were observed. T hese results suggest that Hoxc-4 is required for specifying cervical a nd thoracic vertebral identity. (C) 1996 Academic Press, Inc.