The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3.
Reduced Coat 2 (Rco2) is an ENU-induced mutation affecting hair follicle morphogenesis by an abnormal and protracted catagen. We describe chromosomal mapping and molecular identification of the autosomal dominant Rco2 mutation. The Rco2 critical region on mouse chromosome 11 encompasses the alopecia loci, Bareskin (Bsk), Rex-denuded (Re(den)), Recombination induced mutation 3 (Rim3), and Defolliculated (Dfl). Recently, the gasdermin (Gsdm) gene was described as predominantly expressed in skin and gastric tissues. We provide evidence for a murine-specific gene cluster consisting of Gsdm and two closely related genes which we designate as Gsdm2 and Gsdm3. We show that Gsdm3 reflects a mutation hotspot and that Gsdm3 mutations cause alopecia in Rco2, Re(den), and Bsk mice. We infer a role of Gsdm3 during the catagen to telogen transition at the end of hair follicle morphogenesis and the formation of hair follicle-associated sebaceous glands.
Department of Anatomy, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
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F
Runkel
A
A
Marquardt
C
C
Stoeger
E
E
Kochmann
D
D
Simon
B
B
Kohnke
D
D
Korthaus
F
F
Wattler
H
H
Fuchs
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M
Hrabé de Angelis
G
G
Stumm
M
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Nehls
S
S
Wattler
T
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Franz
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Augustin
D000483:Alleles; D000505:Alopecia / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D005799:Genes, Dominant / Q000235:genetics; D018859:Hair Follicle / Q000254:growth & development*; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000032:analysis / Q000378:metabolism; D012627:Sebaceous Glands / Q000254:growth & development; D012867:Skin / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D000094524:Gasdermins
D009363:Neoplasm Proteins; D011506:Proteins; D012313:RNA; C413482:Gsdma protein, mouse; D000094524:Gasdermins; C499122:Gsdma2 protein, mouse; C499121:Gsdma3 protein, mouse