Document Type

Article

Publication Date

7-20-2020

Keywords

JMG, JAXCC

JAX Source

PLoS One 2020 Jul 20; 15(7):e0235295

Volume

15

Issue

7

First Page

0235295

Last Page

0235295

ISSN

1932-6203

PMID

32687504

DOI

https://doi.org/10.1371/journal.pone.0235295

Grant

AR049288,CA034196

Abstract

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.

Comments

The authors thank Zoe Reifsnyder for assistance with the figures and Nicholas E. Gott in the Histopathology Scientific Service for performing the histology and immunohistochemistry.

This is an open access article distributed under the terms of the Creative Commons Attribution License.

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