Developmental and growth defects in mice with combined deficiency of CK2 catalytic genes
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The CK2 α and α′ catalytic gene products have overlapping biochemical activity, but in vivo, their functions are very different. Deletion of both alleles of CK2α leads to mid-gestational embryonic lethality, while deletion of both alleles of CK2α′ does not interfere with viability or development of embryos; however, adult CK2α′−/−males are infertile. To further elucidate developmental roles of CK2, and analyze functional overlap between the two catalytic genes, mice with combined knockouts were bred. Mice bearing any two CK2 catalytic alleles were phenotypically normal. However, inheritance of a single CK2α allele, without either CK2α′ allele, resulted in partial embryonic lethality. Such mice that survived through embryogenesis were smaller at birth than littermate controls, and weighed less throughout life. However, their cardiac function and lifespan were normal. Fibroblasts derived from CK2α+/−CK2α′−/− embryos grew poorly in culture. These experiments demonstrate that combined loss of one CK2α allele and both CK2α′ alleles leads to unique abnormalities of growth and development.
KeywordsProtein kinase CK2 Casein kinase II Homologous recombination Mouse embryonic fibroblast
This study was supported by NCI R01 CA71796 (DCS). The authors acknowledge the assistance of Patrick Hogan with animal husbandry, Drs. Ravi Jasuja and GianlucaToraldo in the Metabolic Phenotyping Core for assistance with the NMR analysis, members of the Seldin laboratory, and Dr. Isabel Dominguez for helpful discussions.
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