The WD domain of Atg16l1 crucial for LC3-associated phagocytosis is not required for preserving skin barrier function in mice

Conway, Shannon, Jefferson, Matthew, Warren, Derek T., Wileman, Thomas and Morris, Christopher J. (2024) The WD domain of Atg16l1 crucial for LC3-associated phagocytosis is not required for preserving skin barrier function in mice. Journal of Investigative Dermatology Innovations, 4 (4).

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Abstract

The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 (Δ WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection. In this study, the Δ WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and Δ WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged Δ WD but not wild-type mice. In summary, the LAP-deficient Δ WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.

Item Type: Article
Additional Information: Data Availability Statement: No datasets were generated or analyzed during this study. Data related to this article will be made available by the authors without undue reservation.
Uncontrolled Keywords: autophagy,barrier function,epidermal structure,dermatology ,/dk/atira/pure/subjectarea/asjc/2700/2708
Faculty \ School: Faculty of Science
Faculty of Science > School of Pharmacy

Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 29 Apr 2024 12:30
Last Modified: 06 Jun 2024 15:27
URI: https://ueaeprints.uea.ac.uk/id/eprint/95036
DOI: 10.1016/j.xjidi.2024.100283

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