The function of Maid (GCIP), a cyclinD-binding helix-loop-helix protein, was analyzed by targeted disruption in mice. We show that Maid function is not required for normal embryonic development. However, older Maid-deficient mice - in contrast to wild-type controls - develop hepatocellular carcinomas. Therefore, we studied the role of Maid during cell cycle progression after partial hepatectomy (PH). Lack of Maid expression after PH was associated with a delay in G1/S-phase progression as evidenced by delayed cyclinA expression and DNA replication in Maid-deficient mice. However, at later time points liver mass was restored normally. Conclusion: These results indicate that Maid is involved in G1/S-phase progression of hepatocytes, which in older animals is associated with the development of liver tumors.
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