TARGETED DISRUPTION OF MOUSE CENTROMERE PROTEIN-C GENE LEADS TO MITOTIC DISARRAY AND EARLY EMBRYO DEATH

Centromere protein C (CENPC) is a key protein that has been localized to the inner kinetochore plate of active mammalian centromeres, Using gene targeting techniques, we have disrupted the mouse Cenpc gene and shown that the gene is essential for normal mouse embryonic developmen t, Heterozygous mice carrying one functional copy of the gene are heal thy and fertile, whereas homozygous embryos fail to thrive, In these e mbryos, mitotic arrest and gross morphological degeneration become app arent as early as the morula stage of development, The degenerating em bryos demonstrate highly irregular cell and nuclear morphologies, incl uding the presence of a large number of micronuclei, Mitotic chromosom es of these embryos display a scattered and often highly condensed con figuration and do not segregate in an ordered fashion, These results d escribing the phenotype of the mutant mouse embryos indicate that CENP C has a direct role in the mitotic progression from metaphase to anaph ase.