Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression

doi:10.1007/s11684-019-0722-8

Frontiers of Medicine

2020, Vol. 14

Issue (3): 305-317 https://doi.org/10.1007/s11684-019-0722-8

本期目录

Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression

Jun Yang¹, Lianqing Wang^1,², Yingzhi Huang¹, Keqiang Liu¹, Chaoxia Lu¹, Nuo Si¹, Rongrong Wang¹, Yaping Liu¹(

), Xue Zhang¹(

)

¹. McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
². Center of Translational Medicine, Central Hospital of Zibo, Shandong University, Zibo 255036, China

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Abstract：

Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in g-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstn^flox/flox;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1b, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstn^flox/flox;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.

Key words： acne inversa mouse model interleukin 1 family, member 6 small proline rich protein 2D key inflammatory cytokine

收稿日期: 2019-05-16 出版日期: 2020-06-08

Corresponding Author(s): Yaping Liu,Xue Zhang

引用本文:

. [J]. Frontiers of Medicine, 2020, 14(3): 305-317.
Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang. Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression. Front. Med., 2020, 14(3): 305-317.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-019-0722-8
https://academic.hep.com.cn/fmd/CN/Y2020/V14/I3/305

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