An autosomal dominant alteration in Lbr splicing, when expressed in the context of a hemizygous lupus-prone NZW genetic background, elicited the induction of several autoantibodies, including anti-modified histones, IgG2 antibodies recognizing chromatin, and IgM directed against calreticulin, as well as moderate-to-severe kidney disease and splenomegaly, that was sex-restricted to only the female F1 progeny. Here, CALR is linked to Splenomegaly.