Fatal autoimmunity results from the conditional deletion of Snai2 and Snai3.

•A novel mouse strain was created with conditional hematopoietic deletion of the Snai2 and Snai3 genes (cDKO).•The cDKO animal dies weeks after birth from acute autoimmune responses.•The cDKO animal possesses high serum levels of autoreactive IgM and IgG.•The autoimmunity of cDKO animal is reversed with the addition of wild type T regulatory cells.•Loss of tolerance and generation of autoantibodies is intrinsic to cDKO bone marrow-derived cells.