PAXX and Xlf interplay revealed by impaired CNS development and immunodeficiency of double KO mice.
Cell Death Differ
; 25(2): 444-452, 2018 02.
Article
in En
| MEDLINE
| ID: mdl-29077092
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 TCRß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Central Nervous System
/
DNA-Binding Proteins
/
Immunologic Deficiency Syndromes
Limits:
Animals
Language:
En
Journal:
Cell Death Differ
Year:
2018
Document type:
Article
Affiliation country:
France