The WD Domain of Atg16l1 Crucial for LC3-Associated Phagocytosis Is Not Required for Preserving Skin Barrier Function in Mice

Shannon Conway , Matthew Jefferson , Derek T. Warren , Thomas Wileman , Christopher J. Morris
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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.

Atg16l1的WD结构域对LC3相关吞噬功能至关重要,但它并不是保护小鼠皮肤屏障功能所必需的
皮肤是一个多功能器官,在内外环境之间形成一道屏障,从而起到抵御外在因素的作用。自噬与表皮分化和维护皮肤稳态有关。LC3相关吞噬(LAP)利用了自噬的部分而非全部成分。Atg16l1 (Δ WD)小鼠模型缺乏LAP所需的WD40结构域,已被广泛用于研究LAP缺乏和自噬对组织稳态和感染反应的影响。野生型小鼠和Δ WD小鼠1岁时的皮肤组织学显示,尾部皮肤真皮层存在细微的形态差异。RT-qPCR和Western印迹分析表明,不同基因型的关键角蛋白表达没有差异。通过染料渗透试验评估皮肤屏障的形成,结果表明两种基因型的小鼠在胚胎 18.5 天时皮肤屏障完全正常形成。皮肤的生物力学分析表明,老龄Δ WD小鼠的皮肤弹性下降,而野生型小鼠的皮肤弹性则没有下降。总之,LAP缺陷的Δ WD小鼠在皮肤组织学和与年龄相关的生物力学变化方面表现出微妙的改变。
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