Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis

R. E. Seymour, M. G. Hasham, G. A. Cox, L. D. Shultz, Harm HogenEsch, D. C. Roopenian, J. P. Sundberg

Research output: Contribution to journalArticle

117 Citations (Scopus)

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 cpdmDem, 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.

Original languageEnglish (US)
Pages (from-to)416-421
Number of pages6
JournalGenes and Immunity
Volume8
Issue number5
DOIs
StatePublished - Jul 2007
Externally publishedYes

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Dermatitis
Immune System
Inflammation
Mutation
Genes
Proteins
Enteric Nervous System
Post-Synaptic Density
Neurotransmitter Agents
sharpin
Protein Domains
Genome
Phenotype
Brain

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis. / Seymour, R. E.; Hasham, M. G.; Cox, G. A.; Shultz, L. D.; HogenEsch, Harm; Roopenian, D. C.; Sundberg, J. P.

In: Genes and Immunity, Vol. 8, No. 5, 07.2007, p. 416-421.

Research output: Contribution to journalArticle

Seymour, R. E. ; Hasham, M. G. ; Cox, G. A. ; Shultz, L. D. ; HogenEsch, Harm ; Roopenian, D. C. ; Sundberg, J. P. / Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis. In: Genes and Immunity. 2007 ; Vol. 8, No. 5. pp. 416-421.
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