DSG3 and acquired polycythemia vera: Later, the need to study the mechanisms leading to the generation of pathogenic autoantibodies in PV drove the development of an active disease model: Dsg3−/− mice, lacking self-tolerance against naturally expressed Dsg3 (Koch et al., 1997), were immunized against Dsg-3 to generate a source of Dsg3-reactive T and B cells, which were then isolated and injected into immune-deficient (Rag2−/−) but Dsg3+/+ recipients to induce a Dsg3-specific autoimmune response in vivo (Amagai et al., 2000; Tsunoda et al., 2003; Aoki-Ota et al., 2004).