Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene targeting

PSMC3 and PSMC4, components of the 19S complex of the 26S proteasome, show a significant degree of amino acid similarity, especially in the conserved ATPase domain (CAD). In this study, we characterized the mouse Psmc3 and Psmc4 genes. The genomic structures of both genes showed a significant degree of similarity. The Psmc3 gene was composed of 12 coding exons, whereas the Psmc4 gene had 11 exons. Exons encoding the leucine zipper domain and CAD were identical in number between the Psmc3 and Psmc4 genes. The Psmc3 gene mapped to mouse chromosome 2, whereas Psmc4 mapped to chromosome 7. We further addressed the biological roles of Psmc3 and Psmc4 through the generation of gene targeted mice. Both Psmc3- and Psmc4-deficient mice died before implantation, displaying defective blastocyst development. These findings indicate that Psmc3 and Psmc4 have similar and essential roles in early embryogenesis and further that both ATPases have noncompensatory functions in vivo.