The alpha catalytic subunit of protein kinase CK2 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 (CK2alpha and/or CK2alpha') and two CK2beta 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 CK2beta gene is required for early embryonic development, while the CK2alpha' subunit appears to be essential only for normal spermatogenesis. We have used homologous recombination to disrupt the CK2alpha gene in the mouse germ line. Embryos lacking CK2alpha have a marked reduction in CK2 activity in spite of the presence of the CK2alpha' subunit. CK2alpha(-/-) 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, CK2alpha appears to play an essential and uncompensated role in mammalian development.
Lou
David Y
DY
Boston University Medical Center, 650 Albany Street, Boston, MA 02118, USA.
Dominguez
Isabel
I
Toselli
Paul
P
Landesman-Bollag
Esther
E
O'Brien
Conor
C
Seldin
David C
DC
D000818:Animals; D015415:Biomarkers; D047390:Casein Kinase II / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006321:Heart / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D015415:Biomarkers; D021122:Protein Subunits; D012333:RNA, Messenger; D047390:Casein Kinase II