PXD035881-1

PXD035881 is an original dataset announced via ProteomeXchange.

Title	Neurofibromatosis type 1-dependent alterations in mouse microglia function are not cell-intrinsic
Description	We previously discovered a sex-by-genotype defect in microglia function using a germline heterozygous knockout mouse model of Neurofibromatosis type 1 (Nf1+/- mice), in which only microglia from male Nf1+/- mice exhibited defects in purinergic signaling. Herein, we leveraged an unbiased proteomic approach to demonstrate that male, but not female, heterozygous Nf1+/- microglia exhibit differences in protein expression, which largely reflect pathways involved cytoskeletal organization. In keeping with potential defects in cytoskeletal function, only male Nf1+/- microglia had reduced process arborization and surveillance capacity. Next, to determine whether these microglial defects were cell autonomous or reflected adaptive responses to Nf1 heterozygosity in other cells in the brain, we generated conditional microglia Nf1-mutant knockout mice by intercrossing Nf1flox/flox with Cx3cr1-CreER mice (Nf1flox/wt; Cx3cr1-CreER mice, Nf1MG+/- mice). Surprisingly, neither male nor female Nf1MG+/- mouse microglia had impaired process arborization or surveillance capacity. In contrast, when Nf1 heterozygosity was generated in neurons, astrocytes and oligodendrocytes by intercrossing Nf1flox/flox with hGFAP-Cre mice (Nf1flox/wt; hGFAP-Cre mice, Nf1GFAP+/- mice), the microglia defects found in Nf1+/- mice were recapitulated. Collectively, these data reveal that Nf1+/- sexually dimorphic microglia abnormalities are likely not cell-intrinsic properties, but rather reflect a response to Nf1 heterozygosity in other brain cells.
HostingRepository	PRIDE
AnnounceDate	2023-05-10
AnnouncementXML	Submission_2023-05-10_13:24:46.264.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	OliverPopp
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	2022-08-08 09:48:33	ID requested
⏵ 1	2023-05-10 13:24:47	announced
2	2023-11-14 08:46:44	announced	2023-11-14: Updated project metadata.

Logiacco F, Grzegorzek LC, Cordell EC, Popp O, Mertins P, Gutmann DH, Kettenmann H, Semtner M, type 1-dependent alterations in mouse microglia function are not cell-intrinsic. Acta Neuropathol Commun, 11(1):36(2023) [pubmed]

submitter keyword: purinergic signaling, sex differences,neurofibromin, NF1, cortex, microglia, genetically engineered mice

MarcusSemtner
contact affiliation	Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
contact email	Marcus.Semtner@mdc-berlin.de
lab head
OliverPopp
contact affiliation	MDC Berlin
contact email	oliver.popp@mdc-berlin.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/2023/05/PXD035881

PRIDE project URI

• PRIDE
  1. PXD035881
     1. Label: PRIDE project
     2. Name: Neurofibromatosis type 1-dependent alterations in mouse microglia function are not cell-intrinsic