Molecular cloning and characterization of the INK4a and ARF genes in naked mole-rat  [in Japanese]

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Author(s)

    • Miyawaki Shingo
    • Biomedical Animal Research Laboratory, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan|Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    • Kawamura Yoshimi
    • Biomedical Animal Research Laboratory, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan
    • Hachiya Tsuyoshi
    • Iwate Tohoku Medical Megabank Organization Iwate Medical University, Iwate, Japan
    • Shimizu Atsushi
    • Iwate Tohoku Medical Megabank Organization Iwate Medical University, Iwate, Japan
    • Miura Kyoko
    • Biomedical Animal Research Laboratory, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan

Abstract

The naked mole-rat (NMR) is the world's longest-living rodent, with a maximum lifespan of longer than 31 years without any evidence of neoplastic disease. Recently, the NMR has come to be regarded as a useful animal model for the study of longevity and cancer resistance. Sequencing analysis of the NMR genome revealed the existence of species-specific changes in the predicted sequence of the INK4a and ARF tumor suppressors, suggesting the possibility that these two genes might have important roles in NMR's unique longevity and cancer resistance. Here, we report the molecular cloning and characterization of the INK4a and ARF genes <I>in vitro</I>. To investigate the expression and function of the INK4a and ARF genes in NMR, we generated several research tools, including antibodies, real-time PCR primer sets, and overexpression and knockdown vectors. Our results showed that endogenous expression of INK4a and ARF was upregulated in NMR fibroblasts treated with DNA-damaging agents or after serial passaging. In addition, overexpression of INK4a or ARF caused cell cycle arrest in both NMR fibroblasts and mouse NIH-3T3 cells. These results suggest INK4a and ARF execute a conserved function as cell cycle inhibitors in NMR. The research tools developed in the present study will be useful for exploring the specific function of INK4a and ARF genes in the unique longevity and cancer-resistant phenotype of NMRs.

Journal

  • Inflammation and Regeneration

    Inflammation and Regeneration 35(1), 042-050, 2015

    The Japanese Society of Inflammation and Regeneration

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