Direct-in-NOD genetic ablation of Bcl3 leads to complete type 1 diabetes protection.

ABSTRACT: It was previously reported that genetic ablation of the NF-κB atypical inhibitor Bcl3 through congenic introduction of a 129P2-embryo derived knockout allele (Bcl3tm1Ver) accelerated autoimmune diabetes in the NOD mouse model. Conversely, we found that direct CRISPR-mediated ablation of this gene in the NOD/ShiLtDvs substrain completely inhibited diabetes development. Our CRISPR approach excised exons 3-7 within the NOD Bcl3 gene. These new NOD-Bcl3-/- mice had very low levels of insulitis, indicating protective mechanisms elicited early in the disease process. Dissimilar to reports of Bcl3 ablation in nonautoimmune C57BL/6-background mice, we found that splenic and lymph node B cells were not reduced. However, splenic T2 and MZ cells were increased with a disruption of B-cell follicle for

SUBMITTER: Racine JJ 

PROVIDER: S-EPMC12646068 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature