Loss of FAS/FASL signalling does not reduce apoptosis in Sharpin null mice

• Published in: Experimental dermatology Vol. 26; no. 9; pp. 820 - 822
• Main Authors: Potter, Christopher S., Silva, Kathleen A., Kennedy, Victoria E., Stearns, Timothy M., HogenEsch, Harm, Sundberg, John P., Seykora, John
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.09.2017
• Subjects: Apoptosis; cpdm; Dermatitis; Esophagus; Fas; Fasl; FasL protein; Keratinocytes; Leukocytes (eosinophilic); Mutation; Rodents; SHARPIN; Signal transduction; Skin diseases; Tumor necrosis factor; Tumor necrosis factor receptors; cpdm; Fas; apoptosis; SHARPIN; Fasl
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.13289

Mice with mutations in SHANK‐associated RH domain interactor (Sharpin) develop a hypereosinophilic auto‐inflammatory disease known as chronic proliferative dermatitis. Affected mice have increased apoptosis in the keratinocytes of the skin, oesophagus and forestomach driven by extrinsic TNF receptor‐mediated apoptotic signalling pathways. FAS receptor signalling is an extrinsic apoptotic signalling mechanism frequently involved in inflammatory skin diseases. Compound mutations in Sharpin and Fas or Fasl were created to determine whether these death domain proteins influenced the cutaneous phenotype in Sharpin null mice. Both Sharpin/Fas and Sharpin/Fasl compound mutant mice developed an auto‐inflammatory phenotype similar to that seen in Sharpin null mice, indicating that initiation of apoptosis by FAS signalling is likely not involved in the pathogenesis of this disease.