Version 1
: Received: 5 September 2020 / Approved: 6 September 2020 / Online: 6 September 2020 (15:50:10 CEST)
How to cite:
Castaneda-Zegarra, S.; Zhang, Q.; Alirezaylavasani, A.; Fernandez-Berrocal, M.; Yao, R.; Oksenych, V. Leaky Severe Combined Immunodeficiency in Mice Lacking Non-homologous End Joining Factors XLF and MRI. Preprints2020, 2020090145. https://doi.org/10.20944/preprints202009.0145.v1
Castaneda-Zegarra, S.; Zhang, Q.; Alirezaylavasani, A.; Fernandez-Berrocal, M.; Yao, R.; Oksenych, V. Leaky Severe Combined Immunodeficiency in Mice Lacking Non-homologous End Joining Factors XLF and MRI. Preprints 2020, 2020090145. https://doi.org/10.20944/preprints202009.0145.v1
Castaneda-Zegarra, S.; Zhang, Q.; Alirezaylavasani, A.; Fernandez-Berrocal, M.; Yao, R.; Oksenych, V. Leaky Severe Combined Immunodeficiency in Mice Lacking Non-homologous End Joining Factors XLF and MRI. Preprints2020, 2020090145. https://doi.org/10.20944/preprints202009.0145.v1
APA Style
Castaneda-Zegarra, S., Zhang, Q., Alirezaylavasani, A., Fernandez-Berrocal, M., Yao, R., & Oksenych, V. (2020). Leaky Severe Combined Immunodeficiency in Mice Lacking Non-homologous End Joining Factors XLF and MRI. Preprints. https://doi.org/10.20944/preprints202009.0145.v1
Chicago/Turabian Style
Castaneda-Zegarra, S., Rouan Yao and Valentyn Oksenych. 2020 "Leaky Severe Combined Immunodeficiency in Mice Lacking Non-homologous End Joining Factors XLF and MRI" Preprints. https://doi.org/10.20944/preprints202009.0145.v1
Abstract
Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf-/-Mri-/-Trp53+/-and Xlf-/-Paxx-/-Trp53+/-mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.
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.
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