Skip to Main content Skip to Navigation
Journal articles

An in vivo study of the impact of deficiency in the DNA repair proteins PAXX and XLF on development and maturation of the hemolymphoid system: Combined PAXX and Xlf deficiency: an in vivo study

Abstract : The repair of DNA double strand breaks (DSBs) by the non-homologous end-joining pathway (NHEJ) is central for the proper development of the adaptive immune system. This repair pathway involves eight factors, including XRCC4-like factor (XLF)/Cernunnos and the paralog of XRCC4 and XLF, PAXX non-homologous end-joining factor (PAXX). Xlf-/- and Paxx-/- mice are viable and exhibit only a mild immunophenotype. However, mice lacking both PAXX and XLF are embryonic lethal because postmitotic neurons undergo massive apoptosis in embryos. To decipher the roles of PAXX and XLF in both V(D)J recombination and immunoglobulin class switch recombination (CSR), here, using Cre/lox-specific deletion to prevent the double-KO embryonic lethality, we developed two mouse models of a conditional Xlf KO in a Paxx-/- background. Cre expressed under the control of the iVav or CD21 promoter enabled Xlf deletion in early hematopoietic progenitors and splenic mature B cells, respectively. We demonstrate the XLF and PAXX interplay during V(D)J recombination in vivo, but not during CSR for which PAXX appeared to be fully dispensable. A Xlf/Paxx-double KO in hematopoietic progenitors resulted in a shorter lifespan associated with the onset of thymic lymphomas, revealing a genome caretaking function of XLF/PAXX.
Complete list of metadatas

Cited literature [33 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02481526
Contributor : Jean-Pierre de Villartay <>
Submitted on : Monday, February 17, 2020 - 3:09:09 PM
Last modification on : Thursday, April 9, 2020 - 11:56:37 AM
Document(s) archivé(s) le : Monday, May 18, 2020 - 4:50:54 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Stefania Musilli, Vincent Abramowski, Benoit Roch, Jean-Pierre de Villartay. An in vivo study of the impact of deficiency in the DNA repair proteins PAXX and XLF on development and maturation of the hemolymphoid system: Combined PAXX and Xlf deficiency: an in vivo study. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2020, pp.jbc.AC119.010924. ⟨10.1074/jbc.AC119.010924⟩. ⟨inserm-02481526⟩

Share

Metrics

Record views

158