Isolation and characterization of the murine homolog of the human EXT2 multiple exostoses gene.

Multiple exostoses is a polygenic disease of bone formation and development characterized by the presence of cartilage-capped osseous projections emanating from the end of the long bones. Two members of a recently defined multigene family of proteins (EXT1 and 2) were shown to be involved in this disease. To investigate the evolutionary relatedness of EXT genes across species we isolated the mouse EXT2 cDNA. As in the human counterpart, the mouse EXT2 cDNA contains an open reading frame of 2154 bp encoding a predicted protein of 718 amino acids. The nucleic acid sequence is 87% identical to the human EXT2 transcript, resulting in an amino acid sequence which is 95% identical to the human protein. The mouse EXT2 gene also shows significant sequence similarity to the mouse and human EXT1 gene. Northern blot analysis shows that this gene is expressed in early stages of embryonic development, and in situ hybridizations suggest that EXT2 plays a role in limb development. The identification of the mouse EXT2 gene will allow functional analysis through insertional inactivation and reverse genetics in mice in order to better understand the formation of exostoses during bone formation.