In the present study, we focused on examining the role of ERα in mediating the female sex bias in the actions of the lupus susceptibility loci Sle1a and Sle1b. Although Sle1a-induced T cell hyperactivation shows a female sex bias, this phenotype is not modulated by disruption of ERα indicating that the female sex bias is not dependent upon ERα signaling. The gene discussed is ESR1; the disease is systemic lupus erythematosus.