Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis.
Amino-Acid-Sequence, Animals, Dermatitis, Female, Inflammation, Lymphoid-Tissue, Mice, Mice-Inbred-C57BL, Molecular-Sequence-Data, Mutation, Nerve-Tissue-Proteins
Genes Immun 2007 Jul; 8(5):416-21.
Homologues of the SHARPIN (SHANK-associated RH domain-interacting protein) gene have been identified in the human, rat and mouse genomes. SHARPIN and its homologues are expressed in many tissues. SHARPIN protein forms homodimers and associates with SHANK in the post-synaptic density of excitatory neurotransmitters in the brain. SHARPIN is hypothesized to have roles in the crosslinking of SHANK proteins and in enteric nervous system function. We demonstrate that two independently arising spontaneous mutations in the mouse Sharpin gene, cpdm and cpdm(Dem), cause a chronic proliferative dermatitis phenotype, which is characterized histologically by severe inflammation, eosinophilic dermatitis and defects in secondary lymphoid organ development. These are the first examples of disease-causing mutations in the Sharpin gene and demonstrate the importance of SHARPIN protein in normal immune development and control of inflammation.
Seymour, R E.; Hasham, M G.; Cox, G A.; Shultz, L D.; Hogenesch, H; Roopenian, D C.; and Sundberg, J P., "Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis." (2007). Faculty Research 2000 - 2009. 1569.