Proper development of the immune system is an intricate process dependent on 
many factors, including an intact DNA damage response. The DNA double-strand 
break signaling kinase ATM and its cofactor NBS1 are required during T cell 
development and for the maintenance of genomic stability. The role of a second 
ATM cofactor, ATMIN (also known as ASCIZ) in T cells is much less clear, and 
whether ATMIN and NBS1 function in synergy in T cells is unknown. Here, we 
investigate the roles of ATMIN and NBS1, either alone or in combination, using 
murine models. We show loss of NBS1 led to a developmental block at the 
double-positive stage of T cell development, as well as reduced TCRα 
recombination, that was unexpectedly neither exacerbated nor alleviated by 
concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA 
damage that drove spontaneous peripheral T cell hyperactivation, proliferation 
as well as excessive production of proinflammatory cytokines and chemokines, 
leading to a highly inflammatory environment. Intriguingly, the disease causing 
T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted 
in severe intestinal inflammation, colitis and premature death. Our findings 
reveal a novel model for an intestinal bowel disease phenotype that occurs upon 
combined loss of the DNA repair cofactors ATMIN and NBS1.