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The CDK11p110 protein kinases are part of large-molecular-weight complexes that also contain RNA polymerase II, transcriptional elongation factors, and general pre-mRNA splicing factors. CDK11p110 isoforms may therefore couple transcription and pre-mRNA splicing by their effect(s) on certain proteins required for these processes. The CDK11p58 kinase isoform is generated from the CDK11p110 mRNA through the use of an internal ribosome entry site in a mitosis-specific manner, suggesting that this kinase may regulate the cell cycle during mitosis. The in vivo role and necessity of CDK1Vp110/p58 kinase function during mammalian development were examined by generating CDK1Fp110/p58-null mice through targeted disruption of the corresponding gene using homologous recombination. While heterozygous mice develop normally, disruption of both CDK1Vp110/p58 alleles results in early embryonic lethality due to apoptosis of the blastocyst cells between 3.5 and 4 days postcoitus. Cells within these embryos exhibit both proliferative defect(s) and a mitotic arrest. These results are consistent with the proposed cellular functions of the CDK11p110/p58 kinases and confirm that the CDK11p110/p58 kinases are essential for cellular viability as well as normal early embryonic development. [ABSTRACT FROM AUTHOR]