title: Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland.
abstract: Defolliculated (Dfl) is a spontaneous mouse mutant with a hair-loss phenotype that includes altered sebaceous gland differentiation, short hair shafts, aberrant catagen stage of the hair cycle, and eventual loss of the hair follicle. Recently a similar mutant, finnegan (Fgn), with an identical phenotype was discovered during a phenotypic screen for mutations induced by chemical mutagenesis. The gene underlying the phenotype of both finnegan and defolliculated has been mapped to chromosome 11 and here we show that both mice harbor mutations in gasdermin 3 (Gsdm3), a gene of unknown function. Gsdm3(Dfl) is a B2 insertion near the 3' splice site of exon 7 and Gsdm3(Fgn) is a point mutation T278P. To investigate the role of the gasdermin gene family an antiserum was raised to a peptide highly homologous to all three mouse gasdermins and human gasdermin. Immunohistochemical analysis revealed that gasdermins are expressed specifically in cells at advanced stages of differentiation in the upper epidermis, the differentiating inner root sheath and hair shaft and in the most mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous gland, and anal glands. This expression pattern suggests a role for gasdermins in differentiation of the epidermis and its appendages.
authors.affiliation: School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Declan P
authors.initials: DP
authors.lastname: Lunny
authors.forename: Erica
authors.initials: E
authors.lastname: Weed
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
authors.forename: Andreas
authors.initials: A
authors.lastname: Marquardt
authors.forename: Martin
authors.initials: M
authors.lastname: Augustin
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Porter
mesh_terms: D000505:Alopecia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018859:Hair Follicle / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012627:Sebaceous Glands / Q000473:pathology* / Q000503:physiopathology; D012878:Skin Neoplasms; D000094524:Gasdermins
chemical_list: D000906:Antibodies; D011506:Proteins; C499121:Gsdma3 protein, mouse; D000094524:Gasdermins