Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by skin inflammation

Am J Pathol. 2012 Feb;180(2):763-74. doi: 10.1016/j.ajpath.2011.10.034. Epub 2011 Dec 5.


Primary cicatricial alopecias (PCAs) are a group of permanent hair loss disorders, of which the pathogenesis is still poorly understood. The alopecia and excoriation (AE) mouse strain is a dominant mutant generated from ethyl nitrosourea mutagenesis. AE mice exhibit a progressive alopecia phenotype similar to that seen in PCAs, resulting from a point mutation in the gasdermin A3 gene. Mutant mice begin to show alopecia on the head from postnatal day 22 and experience complete hair loss by the age of 6 months, along with hyperkeratosis and catagen delay. The results of a histological examination showed that bulge stem cells in AE skin are gradually depleted, as indicated by decreased keratin 15 and CD34 expression, and reduced bromodeoxyuridine label-retaining cells in the AE bulge. In addition, AE mice display an inflammatory condition in the skin from postnatal day 7, including elevated tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels and significantly increased macrophages and dendritic cell number. Immune privilege in the bulge was also compromised in AE skin. Consistently, after treatment with the immunosuppressive agent, cyclosporine A, immune privilege collapse, stem cell destruction, and alopecia phenotype of AE mice were all rescued. Collectively, our data demonstrate that immune-mediated destruction of bulge stem cells plays a crucial role in the pathogenesis of alopecia in AE mice, and this strain might be an interesting model for PCAs, especially for lichen planopilaris.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alopecia / genetics*
  • Alopecia / immunology
  • Alopecia / pathology
  • Animals
  • Cyclosporine / pharmacology
  • Dermatitis / genetics*
  • Dermatitis / immunology
  • Dermatitis / pathology
  • Dermatologic Agents / pharmacology
  • Genotype
  • Hair Follicle / pathology
  • Mice
  • Mice, Inbred Strains
  • Point Mutation / genetics*
  • Proteins / genetics*
  • Stem Cells / immunology
  • Stem Cells / pathology*


  • Dermatologic Agents
  • Gsdma3 protein, mouse
  • Proteins
  • Cyclosporine