Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

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

Genes & Immunity volume 8, pages 416–421 (2007)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. HogenEsch H, Gijbels M, Offerman E, Hooft Jv, Bekkum Dv, Zurcher C . A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. Am J Pathol 1993; 143: 972–982.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. HogenEsch H, Torregrosa SE, Boggess D, Sundberg BA, Carroll J, Sundberg JP . Increased expression of type 2 cytokines in chronic proliferative dermatitis (cpdm) mutant mice and resolution of inflammation following treatment with IL-12. Eur J Immunol 2001; 31: 734–742.

    Article  CAS  Google Scholar 

  3. HogenEsch H, Janke S, Boggess D, Sundberg JP . Absence of Peyer's patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm/cpdm) mice. J Immunol 1999; 162: 3890–3896.

    CAS  PubMed  Google Scholar 

  4. Sundberg JP, Boggess D, Shultz LD, Fijneman R, Demant P, HogenEsch H et al. The chronic proliferative dermatitis mouse mutation (cpdm): mapping of the mutant gene locus. J Exp Anim Sci 2000; 41: 101–108.

    Article  CAS  Google Scholar 

  5. Lim S, Sala C, Yoon J, Park S, Kuroda S, Sheng M et al. Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. Mol Cell Neurosci 2001; 17: 385–397.

    Article  CAS  Google Scholar 

  6. Daigo Y, Takayama I, Ward SM, Sanders KM, Fujino MA . Novel human and mouse genes encoding a shank-interacting protein and its upregulation in gastric fundus of W/WV mouse. J Gastroenterol Hepatol 2003; 18: 712–718.

    Article  CAS  Google Scholar 

  7. Gijbels M, Zurcher C, Kraal G, Elliot G, HogenEsch H, Schijff G et al. Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm). Am J Pathol 1996; 148: 941–950.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Akilesh S, Shaffer DJ, Roopenian D . Customized molecular phenotyping by quantitative gene expression and pattern recognition analysis. Genome Res 2003; 13: 1719–1727.

    Article  CAS  Google Scholar 

  9. Roopenian DC . Global pattern recognition algorithm. World Wide Web. http://www.jax.org/staff/roopenian/labsite/gene_expression.html2005.

Download references

Acknowledgements

This work was supported by grants from the National Institutes of Health (Grant no. AI060707; AR49288; CA34196). We thank Drs D Serreze and K Johnson for their critical review of this manuscript, Drs E Kim and M Lipoldova for contributing materials mentioned in the text, and D Shaffer, A Brown and J Bubier for technical assistance with real-time QPCR arrays.

Author information

Authors and Affiliations

  1. The Jackson Laboratory, Bar Harbor, ME, USA

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

  2. Department of Veterinary Pathobiology, Purdue University, West Lafayette, IN, USA

    H HogenEsch

Authors
  1. R E Seymour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M G Hasham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G A Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L D Shultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H HogenEsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D C Roopenian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J P Sundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R E Seymour.

Additional information

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seymour, R., Hasham, M., Cox, G. et al. Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis. Genes Immun 8, 416–421 (2007). https://doi.org/10.1038/sj.gene.6364403

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364403

Keywords

This article is cited by

Search

Advanced search

Quick links