PAXX and Xlf interplay revealed by impaired CNS development and immunodeficiency of double KO mice

Abstract : The repair of DNA double-stranded breaks (DNAdsb) through non-homologous end joining (NHEJ) is a prerequisite for the proper development of the central nervous system and the adaptive immune system. Yet, mice with Xlf or PAXX loss of function are viable and present with very mild immune phenotypes, although their lymphoid cells are sensitive to ionizing radiation attesting for the role of these factors in NHEJ. In contrast, we show here that mice defective for both Xlf and PAXX are embryonically lethal owing to a massive apoptosis of post-mitotic neurons, a situation reminiscent to XRCC4 or DNA Ligase IV KO conditions. The development of the adaptive immune system in Xlf(-/-)PAXX(-/-) E18.5 embryos is severely affected with the block of B- and T-cell maturation at the stage of IgH and TCRβ gene rearrangements, respectively. This damaging phenotype highlights the functional nexus between Xlf and PAXX, which is critical for the completion of NHEJ-dependent mechanisms during mouse development.Cell Death and Differentiation advance online publication, 27 October 2017; doi:10.1038/cdd.2017.184.
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Cell Death and Differentiation, Nature Publishing Group, In press, 〈https://www.nature.com/articles/cdd2017184#abstract〉. 〈10.1038/cdd.2017.184〉
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Contributeur : Marie-Christine Vougny <>
Soumis le : lundi 27 novembre 2017 - 10:57:37
Dernière modification le : jeudi 22 mars 2018 - 15:56:03

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Vincent Abramowski, Olivier Etienne, Ramy Elsaid, Junjie Yang, Aurélie Berland, et al.. PAXX and Xlf interplay revealed by impaired CNS development and immunodeficiency of double KO mice. Cell Death and Differentiation, Nature Publishing Group, In press, 〈https://www.nature.com/articles/cdd2017184#abstract〉. 〈10.1038/cdd.2017.184〉. 〈pasteur-01649071〉

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