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Aurora-A kinase is essential for bipolar spindle formation and early development.

Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. We developed a conditional null mutation in the mouse Aurora-A gene to investigate Aurora-A functions in primary cells ex vivo and in vivo. We show here that conditional Aurora-A ablation in cultured embryonic fibroblasts causes impaired mitotic entry and mitotic arrest with a profound defect in bipolar spindle formation. Germ line Aurora-A deficiency causes embryonic death at the blastocyst stage with pronounced cell proliferation failure, mitotic arrest, and monopolar spindle formation. Aurora-A deletion in mid-gestation embryos causes an increase in mitotic and apoptotic cells. These results indicate that murine Aurora-A facilitates, but is not absolutely required for, mitotic entry in murine embryonic fibroblasts and is essential for centrosome separation and bipolar spindle formation in vitro and in vivo. Aurora-A deletion increases apoptosis, suggesting that molecular therapies targeting Aurora-A may be effective in inducing tumor cell apoptosis. Aurora-A conditional mutant mice provide a valuable system for further defining Aurora-A functions and for predicting effects of Aurora-A therapeutic intervention.

Pubmed ID: 19075002 RIS Download

Mesh terms: Alleles | Animals | Apoptosis | Aurora Kinase A | Aurora Kinases | Blastocyst | Cell Proliferation | Embryo Loss | Embryo, Mammalian | Embryonic Development | Female | Fibroblasts | Gene Deletion | Gene Targeting | Mice | Mitosis | Mutation | Ploidies | Pregnancy | Protein-Serine-Threonine Kinases | Spindle Apparatus

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM024364-21
  • Agency: NICHD NIH HHS, Id: R37 HD024462-11
  • Agency: NICHD NIH HHS, Id: R37 HD024462
  • Agency: NCI NIH HHS, Id: R01 CA065773-11A1
  • Agency: NIGMS NIH HHS, Id: R37 GM024364
  • Agency: NIGMS NIH HHS, Id: R01 GM024364
  • Agency: NIGMS NIH HHS, Id: GM24364
  • Agency: NCI NIH HHS, Id: R01 CA065773
  • Agency: NCI NIH HHS, Id: 2-R01-CA065773-11A1

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