Clinical symptoms and disease progression in homozygous Lupo mice. (A-B) Early clinical symptoms with edematous inflammation, proceeding to ulceration, crust formation, and necrosis of 2 digits (B, arrows). (C) Ear destruction by ulcerative inflammation. (D) Radiogram showing the destruction of the distal phalanx of digit 3 in a homozygous mutant mouse. Note the shadow caused by the surrounding edematous soft tissue (arrow). (E) Radiogram of WT control paw. (F) Cumulative fraction free of clinical events for Lupo homozygotes on the C3H background, in outcross/intercross (IC) Rag1^+/+, C3H/BL6 (50%/50%) population used for positional cloning and on the Rag1^-/-, C3H/BL6 (50%/50%) background. On the Rag1^+/+, C3H/BL6 background, the median age of onset was significantly later, and lifetime penetrance was lower than on the C3H or the Rag1^-/-, C3H/BL6 background (Kaplan-Meier with log rank test [P < .001] for C3H/BL6 versus C3H and C3H/BL6 versus Rag1^-/-, C3H/BL6; censored, termination of observation without an event).