Itchy Mice: The Identification of a New Pathway for the Development of Autoimmunity

摘要: Itchy mice possess a loss-of-function mutation in HECT-domain-containing ubiquitin ligase (E3), Itch. Homozygous itchy develop systemic and progressive autoimmune disease that proves lethal beginning at 6 months of age. Numerous targets Itch-mediated ubiquitination have been identified, some these defined physiological roles for Itch signaling T cell anergy differentiation. Studies also allowed the identification novel pathway involved autoimmunity: noncanonical Notch signaling. In carrying an activated Notch1 transgene, there are increased amounts full-length Notch1, which can complex with p56lck PI3K to activate survival signal is mediated by phospho-AKT. This, turn, leads reduction apoptosis thymus may consequences tolerance. A role supported numerous mouse knockout studies, suggests possible new therapeutic approaches treatment disease.