title: Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis.
abstract: 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.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA. rose.seymour@jax.org
authors.forename: R E
authors.initials: RE
authors.lastname: Seymour
authors.forename: M G
authors.initials: MG
authors.lastname: Hasham
authors.forename: G A
authors.initials: GA
authors.lastname: Cox
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: H
authors.initials: H
authors.lastname: Hogenesch
authors.forename: D C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: J P
authors.initials: JP
authors.lastname: Sundberg
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D003872:Dermatitis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C425287:sharpin