PXD046782-1

PXD046782 is an original dataset announced via ProteomeXchange.

Title	Genomic contamination causes NLRP1 hypersensitivity and altered cell surface markerGenomic contamination causes NLRP1 hypersensitivity and altered cell surface marker expression in Nlrp3-/- macrophagesGenomic contamination causes NLRP1 hypersensitivity and altered cell surface marker expression in Nlrp3-/- macrophages
Description	The NLRP1 and NLRP3 inflammasomes are critical immune signaling hubs that drive cytokine release and inflammatory cell death, and have been implicated in the pathogenesis of diverse diseases. Much of our understanding of inflammasome biology stems from experiments performed in transgenic mouse lines. However, the unavoidable retention of highly polymorphic genomic regions in transgenic mice can confound results, leading to false conclusions, and delaying scientific progress and clinical development. Here, we found that the most commonly used NLRP3 deficient mouse strain, unknowingly contains a substantial region of 129 genome proximal to Nlrp3, causing a hypersensitive response to NLRP1 stimulation, altered gene regulation across multiple cell-types, and the misexpression of the key macrophage cell surface marker TIM4, independently of NLRP3 deficiency. Our results demonstrate that phenotypes previously attributed to the loss of NLRP3 expression may in fact be a byproduct of passenger mutations, and that conventional macrophage identification is obsolete. These data, and our validation of a previously unreported conditional Nlrp3 allele, are critical for the immunology community in ensuring correct data interpretation and improving experimental design. Furthermore, they open new questions in how genetically distinct mouse strains regulate inflammasome protein stability and expression to restrict excessive inflammation.
HostingRepository	PRIDE
AnnounceDate	2024-09-16
AnnouncementXML	Submission_2024-09-16_05:25:05.292.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felix Weiss
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-08 05:15:13	ID requested
⏵ 1	2024-09-16 05:25:05	announced

Dataset with its publication pending

submitter keyword: inflammasome, mouse genetics,immunology

Felix Meissner
contact affiliation	Institute of Innate Immunity BMZ-II, Building 12, Room 2G408 University Hospital Bonn, University of Bonn
contact email	felix.meissner@uni-bonn.de
lab head
Felix Weiss
contact affiliation	University Hospital Bonn
contact email	fweiss@uni-bonn.de
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD046782

PRIDE project URI

• PRIDE
  1. PXD046782
     1. Label: PRIDE project
     2. Name: Genomic contamination causes NLRP1 hypersensitivity and altered cell surface markerGenomic contamination causes NLRP1 hypersensitivity and altered cell surface marker expression in Nlrp3-/- macrophagesGenomic contamination causes NLRP1 hypersensitivity and altered cell surface marker expression in Nlrp3-/- macrophages