Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin

Abstract

Experimental Dermatology. 2020;29:548-555. wileyonlinelibrary.com/journal/exd | INTRODUC TI ONOur understanding of skin morphology and lipid composition has benefitted greatly from the use of in vivo animal models. [1][2][3] In particular, mouse models have been proven a valuable tool in skin research as it offers the possibility to genetically manipulate these animals to study the role of specific skin components (eg enzymes, proteins, receptors) and to generate in vivo diseased skin models. [1,2] In research, the back skin and the ear skin of mice are commonly used sites. However, previous studies reported differential effects/ AbstractThe skin of the ear and the back are frequently selected sites in skin research using mouse models. However, distinct responses to treatment have been described between these two sites in several studies. Despite the crucial role of the stratum corneum (SC) in the skin barrier function of both dorsal back and ear skin, it remains unclear whether differences in lipid composition might underlie altered responses.Here, we compared the skin morphology and the barrier lipid composition of the ear with the back skin of wild-type mice. The ear contained more corneocyte layers in the SC and its barrier lipid composition was enriched with sphingosine ceramide subclasses, especially the short ones with a total chain length of 33-34 carbons. The free fatty acid (FFA) profile in the ear skin shifted towards shorter chains, significantly reducing the mean chain length to 23.3 vs 24.7 carbons in the back skin. In line, FFA species in the ear displayed a twofold increase in unsaturation index (P < .001). Gene expression in the ear skin revealed low expression of genes involved in lipid synthesis and uptake, indicating a reduced metabolic activity. Finally, the effects of hypercholesterolaemia on SC FFA composition was compared in ear and back skin of apolipoprotein E knockout (APOE −/− ) mice. Interestingly, the FFA profile in APOE −/− ear skin was minimally affected, while the FFA composition in the back skin was markedly changed in response to hypercholesterolaemia. In conclusion, ear and back skin have distinct barrier lipids and respond differently to elevated plasma cholesterol. K E Y W O R D S apolipoprotein E knockout mice, ceramides, fatty acids, wild-type mice | 549 MARTINS CARDOSO eT Al.phenotypes on ear skin vs the back skin regarding, among others, drug treatment (eg imiquimod-induced psoriasis, allergic contact dermatitis), melanocyte function and tissue regeneration. [4][5][6] The back skin comprises a relatively large area for performing experiments, but in hairy mice it contains a high density of hair follicles (fur) that can complicate the interpretation of the results. [5] In most studies, the fur is shaved to allow skin treatment and analysis. At the same time, the hair follicles may offer an alternative pathway for compound permeation. [7,8] In contrast, the ear represents an easily accessible, but small, skin area with a low density of hair follicles and centrally supported...

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