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Modeling the Study of DNA Damage Responses in Mice

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Mouse Models of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1267))

Abstract

Damaged DNA has a profound impact on mammalian health and overall survival. In addition to being the source of mutations that initiate cancer, the accumulation of toxic amounts of DNA damage can cause severe developmental diseases and accelerate aging. Therefore, understanding how cells respond to DNA damage has become one of the most intense areas of biomedical research in the recent years. However, whereas most mechanistic studies derive from in vitro or in cellulo work, the impact of a given mutation on a living organism is largely unpredictable. For instance, why BRCA1 mutations preferentially lead to breast cancer whereas mutations compromising mismatch repair drive colon cancer is still not understood. In this context, evaluating the specific physiological impact of mutations that compromise genome integrity has become crucial for a better dimensioning of our knowledge. We here describe the various technologies that can be used for modeling mutations in mice and provide a review of the genes and pathways that have been modeled so far in the context of DNA damage responses.

*Julia Specks and Maria Nieto-Soler should be considered as co-first authors.

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Acknowledgments

Work in OF laboratory is supported by the Spanish Ministry of Science (SAF2011-23753), Association for International Cancer Research (12-0229), Fundació La Marató de TV3 (33/C(2013), Howard Hughes Medical Institute, and the European Research Council (ERC-210520). J. S. is a recipient of a predoctoral fellowship from the Spanish Government (FPI-2012). M. N. is funded by a predoctoral fellowship from the La Caixa Foundation. A. J. L. is a recipient of a postdoctoral fellowship from the Spanish Association Against Cancer (AECC).

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    1. Genomic Instability Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro, 3, E-28029, Madrid, Spain

      Julia Specks, Maria Nieto-Soler, Andres J. Lopez-Contreras & Oscar Fernandez-Capetillo

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    1. Julia Specks
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    2. Maria Nieto-Soler
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    3. Andres J. Lopez-Contreras
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    Correspondence to Andres J. Lopez-Contreras .

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    1. Medical University Vienna (MUV) Institute for Cancer Research, Vienna, Austria

      Robert Eferl

    2. Research (LBI-CR), Medical University Vienna (MUV), Center of Physiology and Pharmacology & Ludwig Boltzmann Institute for Cancer, Vienna, Austria

      Emilio Casanova

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    Specks, J., Nieto-Soler, M., Lopez-Contreras, A.J., Fernandez-Capetillo, O. (2015). Modeling the Study of DNA Damage Responses in Mice. In: Eferl, R., Casanova, E. (eds) Mouse Models of Cancer. Methods in Molecular Biology, vol 1267. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2297-0_21

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