The alpha catalytic subunit of protein kinase CKZ is required for mouse embryonic development

Protein kinase CK2 (formerly casein kinase II) is a highly conserved and ubiquitous serine/threonine kinase that is composed of two catalytic subunits (CK2 alpha and/or CK2 alpha') and two CK2 beta regulatory subunits. CK2 has many substrates in cells, and key roles in yeast cell physiology have been uncovered by introducing subunit mutations. Gene-targeting experiments have demonstrated that in mice, the CK2 beta gene is required for early embryonic development, while the CK2 alpha' subunit appears to be essential only for normal spermatogenesis. We have used homologous recombination to disrupt the CK2 alpha gene in the mouse germ line. Embryos lacking CK2 alpha have a marked reduction in CK2 activity in spite of the presence of the CK2 alpha' subunit. CK2 alpha(-/-) embryos die in mid-gestation, with abnormalities including open neural tubes and reductions in the branchial arches. Defects in the formation of the heart lead to hydrops fetalis and are likely the cause of embryonic lethality. Thus, CK2 alpha appears to play an essential and uncompensated role in mammalian development.