Toll-like receptor 7(TLR7) variant Y264H has recently been identified to cause Systemic Lupus Erythematosus (SLE) in human patients. Mice harboring TLR7Y264H mutation in the C57BL/6NCrL background developed spontaneous SLE-like symptoms and organ damage. In order to create clinically relevant mouse models of SLE to evaluate novel therapeutics (especially targeting TLR7), we developed TLR7Y264H mutant mice in both the BALB/c and C57BL/6J background.