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Gene Review

Dsg3  -  desmoglein 3

Mus musculus

Synonyms: 130 kDa pemphigus vulgaris antigen homolog, Desmoglein-3, bal, balding
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Disease relevance of Dsg3

  • Pemphigus is a life-threatening blistering disorder of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein 3 (Dsg3) and Dsg1 [1].
  • PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V gene and isotype usage in PV pathogenesis [2].
  • CONCLUSION: The cDNA sequence and the baculovirus recombinant protein of canine Dsg3 will be useful to characterize the serum autoantibodies in canine PV [3].
  • BACKGROUND: Pemphigus vulgaris (PV) is a blistering skin disease caused by IgG autoantibodies against desmoglein 3 (Dsg3) [4].
  • These findings indicate that the CD40/CD154 interaction is essential for the induction of pathogenic anti-Dsg3 IgG antibodies and that antigen-specific immune-regulatory cells induced by anti-CD154 mAb would hold a therapeutic option for autoimmune diseases [5].

High impact information on Dsg3

  • Protection against pemphigus foliaceus by desmoglein 3 in neonates [6].
  • Antibodies against BP180, Dsg1, and Dsg3, when injected into neonatal mice, induce the BP, PF, and PV disease phenotypes, respectively [7].
  • Splenocytes from the immunized Dsg3(-/-) mice were then adoptively transferred into Rag-2(-/-) immunodeficient mice expressing Dsg3 [8].
  • This IgG bound to Dsg3 in vivo and disrupted the cell-cell adhesion of keratinocytes [8].
  • We injected into Dsg 3-lacking mice the PV IgGs that did not cross-react with the 160-kDa Dsg 1 or its 45-kDa immunoreactive fragment and that showed no reactivity with recombinant Dsg 1 [9].

Chemical compound and disease context of Dsg3


Biological context of Dsg3

  • Collectively, the recipient mice developed the phenotype of PV due to the pathogenic anti-Dsg3 IgG [8].
  • CONCLUSIONS: In PV model mice the antibodies were dominantly raised against the middle to C-terminal extracellular domains of mouse Dsg3 where amino acid sequences are less conserved among desmoglein isoforms and that those antibodies may also be involved in the blister formation [4].
  • Thus, the anti-desmoglein antibody profiles in pemphigus sera and the normal tissue distributions of Dsg1 and Dsg3 determine the sites of blister formation [11].
  • Loss of cell adhesion in Dsg3bal-Pas mice with homozygous deletion mutation (2079del14) in the desmoglein 3 gene [12].
  • The mouse desmoglein 3 gene consisted of 15 exons in chromosome 18 [13].

Anatomical context of Dsg3

  • Intraperitoneal inoculation of the AK23 hybridoma, but not the other AK hybridomas, induced the virtually identical phenotype to that of PV model mice or Dsg3(-/-) mice with typical histology of PV [14].
  • These results suggest that loss of tolerance against Dsg3 in both B and T cells is important for the development of autoimmune state of PV [15].
  • These results indicate that the N-terminal regions of Dsg3 from opposing cells interact at the dense mid-line of desmosomes where EC1 overlaps [16].
  • We demonstrate that, although a Dsg3 mRNA transcript was detectable in Dsg3bal-Pas skin, the corresponding protein for desmoglein 3 was completely absent in the oral mucosal epithelium of homozygous Dsg3bal-Pas compared with that of +/Dsg3bal-Pas mice [12].
  • Three different hybridoma cell lines producing anti-Dsg3 monoclonal antibodies (mAb) were intraperitoneally injected into immunodeficient mice and the precise ultrastructural location of bound IgG between the mucosal epithelial cells in vivo was statistically measured and analyzed [16].

Associations of Dsg3 with chemical compounds

  • Our results contrast markedly with those recently obtained by expressing Dsg3 in epidermis under the involucrin promoter [17].
  • This hypothesis has been confirmed by another group who demonstrated that the bal(J) mutation is due to the insertion of a thymidine in the desmoglein 3 gene, resulting in a premature stop codon [18].

Enzymatic interactions of Dsg3


Regulatory relationships of Dsg3


Other interactions of Dsg3

  • Several murine models of skin inflammation were found to develop autoantibodies to Dsg3 tightly correlated with disease aggravation, especially in MRL lpr/lpr mice [21].
  • We have recently developed an active disease mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3-/- mice into Rag2-/- recipient mice [4].
  • We characterized their epitopes using domain-swapped and point-mutated Dsg1/Dsg3 molecules and examined their pathogenic activities in blister formation in three different assays [22].
  • Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins [23].
  • DSG3 -/- mice had no DSG3 mRNA by RNase protection assay and no Dsg3 protein by immunofluorescence (IF) and immunoblots [24].

Analytical, diagnostic and therapeutic context of Dsg3


  1. Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display. Payne, A.S., Ishii, K., Kacir, S., Lin, C., Li, H., Hanakawa, Y., Tsunoda, K., Amagai, M., Stanley, J.R., Siegel, D.L. J. Clin. Invest. (2005) [Pubmed]
  2. Pathogenic human monoclonal antibody against desmoglein 3. Yeh, S.W., Cavacini, L.A., Bhol, K.C., Lin, M.S., Kumar, M., Duval, M., Posner, M.R., Ahmed, A.R. Clin. Immunol. (2006) [Pubmed]
  3. Cloning of canine desmoglein 3 and immunoreactivity of serum antibodies in human and canine pemphigus vulgaris with its extracellular domains. Nishifuji, K., Amagai, M., Ota, T., Nishikawa, T., Iwasaki, T. J. Dermatol. Sci. (2003) [Pubmed]
  4. Conformational epitope mapping of antibodies against desmoglein 3 in experimental murine pemphigus vulgaris. Anzai, H., Fujii, Y., Nishifuji, K., Aoki-Ota, M., Ota, T., Amagai, M., Nishikawa, T. J. Dermatol. Sci. (2004) [Pubmed]
  5. Tolerance induction by the blockade of CD40/CD154 interaction in pemphigus vulgaris mouse model. Aoki-Ota, M., Kinoshita, M., Ota, T., Tsunoda, K., Iwasaki, T., Tanaka, S., Koyasu, S., Nishikawa, T., Amagai, M. J. Invest. Dermatol. (2006) [Pubmed]
  6. Protection against pemphigus foliaceus by desmoglein 3 in neonates. Wu, H., Wang, Z.H., Yan, A., Lyle, S., Fakharzadeh, S., Wahl, J.K., Wheelock, M.J., Ishikawa, H., Uitto, J., Amagai, M., Stanley, J.R. N. Engl. J. Med. (2000) [Pubmed]
  7. Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases. Li, N., Zhao, M., Hilario-Vargas, J., Prisayanh, P., Warren, S., Diaz, L.A., Roopenian, D.C., Liu, Z. J. Clin. Invest. (2005) [Pubmed]
  8. Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus. Amagai, M., Tsunoda, K., Suzuki, H., Nishifuji, K., Koyasu, S., Nishikawa, T. J. Clin. Invest. (2000) [Pubmed]
  9. Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions. Nguyen, V.T., Ndoye, A., Shultz, L.D., Pittelkow, M.R., Grando, S.A. J. Clin. Invest. (2000) [Pubmed]
  10. Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation. Allen, E., Yu, Q.C., Fuchs, E. J. Cell Biol. (1996) [Pubmed]
  11. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. Mahoney, M.G., Wang, Z., Rothenberger, K., Koch, P.J., Amagai, M., Stanley, J.R. J. Clin. Invest. (1999) [Pubmed]
  12. Loss of cell adhesion in Dsg3bal-Pas mice with homozygous deletion mutation (2079del14) in the desmoglein 3 gene. Pulkkinen, L., Choi, Y.W., Simpson, A., Montagutelli, X., Sundberg, J., Uitto, J., Mahoney, M.G. J. Invest. Dermatol. (2002) [Pubmed]
  13. Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily. Ishikawa, H., Li, K., Tamai, K., Sawamura, D., Uitto, J. Exp. Dermatol. (2000) [Pubmed]
  14. Induction of pemphigus phenotype by a mouse monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3. Tsunoda, K., Ota, T., Aoki, M., Yamada, T., Nagai, T., Nakagawa, T., Koyasu, S., Nishikawa, T., Amagai, M. J. Immunol. (2003) [Pubmed]
  15. Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris. Tsunoda, K., Ota, T., Suzuki, H., Ohyama, M., Nagai, T., Nishikawa, T., Amagai, M., Koyasu, S. Eur. J. Immunol. (2002) [Pubmed]
  16. In vivo ultrastructural localization of the desmoglein 3 adhesive interface to the desmosome mid-line. Shimizu, A., Ishiko, A., Ota, T., Saito, H., Oka, H., Tsunoda, K., Amagai, M., Nishikawa, T. J. Invest. Dermatol. (2005) [Pubmed]
  17. Suprabasal desmoglein 3 expression in the epidermis of transgenic mice results in hyperproliferation and abnormal differentiation. Merritt, A.J., Berika, M.Y., Zhai, W., Kirk, S.E., Ji, B., Hardman, M.J., Garrod, D.R. Mol. Cell. Biol. (2002) [Pubmed]
  18. Vesicle formation and follicular root sheath separation in mice homozygous for deleterious alleles at the balding (bal) locus. Montagutelli, X., Lalouette, A., Boulouis, H.J., Guénet, J.L., Sundberg, J.P. J. Invest. Dermatol. (1997) [Pubmed]
  19. IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model. Shimizu, A., Ishiko, A., Ota, T., Tsunoda, K., Amagai, M., Nishikawa, T. J. Invest. Dermatol. (2004) [Pubmed]
  20. Desmoglein isoform distribution affects stratum corneum structure and function. Elias, P.M., Matsuyoshi, N., Wu, H., Lin, C., Wang, Z.H., Brown, B.E., Stanley, J.R. J. Cell Biol. (2001) [Pubmed]
  21. Involvement of a tissue-specific autoantibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases. Nishimura, H., Strominger, J.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Synergistic pathogenic effects of combined mouse monoclonal anti-desmoglein 3 IgG antibodies on pemphigus vulgaris blister formation. Kawasaki, H., Tsunoda, K., Hata, T., Ishii, K., Yamada, T., Amagai, M. J. Invest. Dermatol. (2006) [Pubmed]
  23. Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins. Roh, J.Y., Stanley, J.R. J. Cell Biol. (1995) [Pubmed]
  24. Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. Koch, P.J., Mahoney, M.G., Ishikawa, H., Pulkkinen, L., Uitto, J., Shultz, L., Murphy, G.F., Whitaker-Menezes, D., Stanley, J.R. J. Cell Biol. (1997) [Pubmed]
  25. Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. Amagai, M., Nishikawa, T., Nousari, H.C., Anhalt, G.J., Hashimoto, T. J. Clin. Invest. (1998) [Pubmed]
  26. Interspecies conservation and differential expression of mouse desmoglein gene family. Mahoney, M.G., Simpson, A., Aho, S., Uitto, J., Pulkkinen, L. Exp. Dermatol. (2002) [Pubmed]
  27. A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice. Aoki-Ota, M., Tsunoda, K., Ota, T., Iwasaki, T., Koyasu, S., Amagai, M., Nishikawa, T. Br. J. Dermatol. (2004) [Pubmed]
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