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Transcriptome profiling of lesional skin from neonate Spink5 constitutive knock-out mice

ABSTRACT: Spink5 constitituve knock-out mice mimic the disease features of Netherton syndrome but die within several hours after birth due to severe skin barrier defect. To characterize the skin barrier and skin inflammation phenotype of this mouse model at the molecular level, we collected back skin samples from mice shortly after their birth.

ORGANISM(S): Mus musculus

PROVIDER: GSE224674 | GEO | 2024/02/05

REPOSITORIES: GEO

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Transcriptome profiling of lesional skin from Spink5 conditional knock-out mice

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Transcriptome profiling of lymph nodes from Spink5 conditional knock-out mice.

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Transcriptome profiling of lesional skin from 3-week-old Tg.hKLK5 mice

Project description:Transgenic mice over-experssing human KLK5 (Tg.hKLK5) in the epidermis develop an inflammatory skin phenotype resembling Netherton syndrome. To characterize the skin inflammation phenotype of this mouse model at the molecular level, we collected back skin samples from young mice at three weeks of age, when the skin phenotype is most severe.

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Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice define disease-relevant pathways

Project description:Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a viable, Spink5 conditional knock-out (cKO) mouse model, allowing to study NS progression. Using comparative transcriptomics and proteomics, we determine a disease molecular profile conserved in mouse models and NS patients. Spink5 cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation of proteases, IL-17, IL-36, IL-20 family cytokines. Furthermore, we show that systemic inflammation in Spink5 cKO mice is associated with thymic atrophy and is driven by innate immunity and IL-17/IL-22 signaling. By comparing skin transcriptomes and proteomes, we uncovered several putative substrates of tissue kallikrein-related proteases (KLKs), demonstrating that KLKs can proteolytically regulate IL-36 pro-inflammatory cytokines. Our study thus provides a conserved molecular framework for NS disease, adding new insights into its mechanisms and therapeutic targets.

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Transcription profiling by array of lesional and non-lesional skin from atopic dermatitis patients and healthy individuals

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