ResearchIn-Press PreviewDermatologyGenetics
Open Access | 10.1172/jci.insight.177588
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Wang, X. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Pan, C. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zheng, L. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Wang, J. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zou, Q. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Sun, P. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zhou, K. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zhao, A. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Cao, Q. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by He, W. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Wang, Y. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Cheng, R. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Yao, Z. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zhang, S. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Zhang, H. in: JCI | PubMed | Google Scholar
1Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China
3Department of Dermatology, Children's Hospital of Fudan University, Shanghai, China
4NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry a, School of Basic Medical Sciences, Fudan University, Shanghai, China
Find articles by Li, M. in: JCI | PubMed | Google Scholar
Published May 21, 2024 - More info
Hypotrichosis is a genetic disorder which characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in ADAM17 gene caused hypotrichosis with woolly hair. Adam17 (p.D647N) knock-in mice model mimicked the hair abnormality in patients. ADAM17 (p.D647N) mutation led to hair follicle stem cells (HFSCs) exhaustion and caused abnormal hair follicles, ultimately resulting in alopecia. Mechanistic studies revealed that ADAM17 binds directly to E3 ubiquitin ligase TRIM47. ADAM17 (p.D647N) variant enhanced the association between ADAM17 and TRIM47, leading to an increase in ubiquitination and subsequent degradation of ADAM17 protein. Furthermore, reduced ADAM17 protein expression affected Notch signaling pathway, impairing the activation, proliferation, and differentiation of HFSCs during hair follicle regeneration. Overexpression of NICD rescued the reduced proliferation ability caused by Adam17 variant in primary fibroblast cells.