PXD039796-1

PXD039796 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice define disease-relevant pathways
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.
HostingRepository	MassIVE
AnnounceDate	2024-04-15
AnnouncementXML	Submission_2024-04-15_07:44:07.561.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Fahrner
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	Q Exactive Plus

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-02 04:13:29	ID requested
⏵ 1	2024-04-15 07:44:08	announced

Publication List

Petrova E, L, ó, pez-Gay JM, Fahrner M, Leturcq F, de Villartay JP, Barbieux C, Gonschorek P, Tsoi LC, Gudjonsson JE, Schilling O, Hovnanian A, Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways. Commun Biol, 7(1):152(2024) [pubmed]

Petrova E, L, ó, pez-Gay JM, Fahrner M, Leturcq F, de Villartay JP, Barbieux C, Gonschorek P, Tsoi LC, Gudjonsson JE, Schilling O, Hovnanian A, Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways. Commun Biol, 7(1):152(2024) [pubmed]

Keyword List

submitter keyword: Netherton syndrome, Mouse model, SPINK5 mice, LC-MS/MS

submitter keyword: Netherton syndrome, Mouse model, SPINK5 mice, LC-MS/MS

Contact List

Prof. Oliver Schilling
contact affiliation	Institute for Surgical Pathology, University Medical Center Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Matthias Fahrner
contact affiliation	University of Freiburg
contact email	matthias.fahrner@uniklinik-freiburg.de
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v05/MSV000091184/