Consistently, RAP99-LPS activated immune cells via TLR4 like E. coli-LPS, because we found RAP99-LPS-mediated weight loss and splenomegaly were significantly suppressed in C3H/HeJ mice, which lack TLR4-mediated signal transduction, but not in control C3H/HeN mice. The gene discussed is TLR4; the disease is Splenomegaly.