Gsdma3 is required for hair follicle differentiation in mice.
Hair follicle differentiation is regulated by multiple signaling pathways. However, the known cellular and molecular mechanisms are limited. Gsdma3 is a novel murine gene and considered to be a mutation hotspot. Six mutants have been reported in Gsdma3 and all these mutants exhibit hair loss and hyperkeratosis phenotypes. In order to verify how the lack of Gsdma3 affects the hair defects, we use alopecia and excoriation mice, a new mouse mutation in this gene, as our research model. This mutation exhibits progressive hair loss, from head to the whole back, and followed by hair regrowth. We test that Gsdma3 is expressed in matrix, inner root sheath, and hair shaft. Ultrastructural and histological analyses show abnormal hair structures and reduced hair keratins in AE mice. The loss of interlocking structures and abnormal constitutive protein indicate defects in anchoring hair shaft in the hair follicle and resisting external forces. Molecular analysis of Gsdma3 deficiency and overexpression shows an Msx2/Foxn1/acidic hair keratin genetic pathway is involved. Thus, Gsdma3 is necessary for normal hair follicle differentiation.
Li
Jin
J
111 Project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing 400044, People's Republic of China.
Zhou
Yue
Y
Yang
Tian
T
Wang
Ning
N
Lian
Xiaohua
X
Yang
Li
L
D000505:Alopecia / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018859:Hair Follicle / Q000002:abnormalities / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism; D000094524:Gasdermins
D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D011506:Proteins; D051881:Receptor, Notch1; C499121:Gsdma3 protein, mouse; D000094524:Gasdermins; C485834:Hoxc13 protein, mouse; C084119:MSX2 protein; C497762:Notch1 protein, mouse; C090140:Whn protein