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Open AccessFeature PaperArticle

Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren

1
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway
2
St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250, Sluppen, 7006 Trondheim, Norway
3
Molecular Biotechnology MS programme, Heidelberg University, 69120 Heidelberg, Germany
4
Department of Biosciences and Nutrition (BioNut), Karolinska Institutet, 14183 Huddinge, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(12), 798; https://doi.org/10.3390/biom9120798
Received: 7 November 2019 / Revised: 23 November 2019 / Accepted: 26 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue DNA Damage Response)
Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.
Keywords: NHEJ; double-strand breaks; mouse model; lymphocyte; neurodevelopment NHEJ; double-strand breaks; mouse model; lymphocyte; neurodevelopment
MDPI and ACS Style

Castañeda-Zegarra, S.; Huse, C.; Røsand, Ø.; Sarno, A.; Xing, M.; Gago-Fuentes, R.; Zhang, Q.; Alirezaylavasani, A.; Werner, J.; Ji, P.; Liabakk, N.-B.; Wang, W.; Bjørås, M.; Oksenych, V. Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren. Biomolecules 2019, 9, 798.

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