Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Sergio Castañeda-Zegarra
ORCID logo ,
Camilla Huse
,
Øystein Røsand
,
Antonio Sarno
,
Mengtan Xing
,
Raquel Gago-Fuentes
,
Qindong Zhang
,
Amin Alirezaylavasani
,
Julia Werner
,
Ping Ji
,
Nina-Beate Liabakk
,
Wei Wang
,
Magnar Bjørås
,
Valentyn Oksenych
* ORCID logo
Version 1 : Received: 23 November 2019 / Approved: 24 November 2019 / Online: 24 November 2019 (15:57:38 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

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 the V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. 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 factors subunits XLF, XRCC4 and 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 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 WT 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

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.