We inserted the chimeric TLRs into the endogenous locus of TLR7 and TLR9, respectively, in lupus-prone MRL/lpr mice and then studied signaling, TLR ligand-inducible gene expression, TLR localization, and, finally, the effect of the TIR domain swaps on lupus-like disease. The gene discussed is TLR7; the disease is systemic lupus erythematosus.