PXD044119

PXD044119 is an original dataset announced via ProteomeXchange.

Title	Loss of the parkinsonism-associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to anormal motor behavior and synaptic defects
Description	Mutations in PARK15, which encodes for the F-box protein FBXO7 have been associated with Parkinsonian Pyramidal syndrome, a rare and complex movement disorder with Parkinsonian symptoms, pyramidal tract signs and juvenile onset. Our previous study showed that systemic loss of Fbxo7 in mice causes motor defects and premature death. We have also demonstrated that FBXO7 has a crucial role in neurons as the specific deletion in tyrosine hydroxylase-positive or glutamatergic forebrain neurons leads to late-onset or early-onset motor dysfunction, respectively. In this study, we examined NEXCre; Fbxo7fl/fl mice, in which Fbxo7 was specifically deleted in glutamatergic projection neurons. The effects of FBXO7 deficiency on striatal integrity were investigated with HPLC and histological analyses. NEX-Cre;Fbxo7fl/fl mice revealed an increase in striatal dopamine concentrations, changes in the glutamatergic, GABAergic and dopaminergic pathways, astrogliosis and microgliosis and little or no neuronal loss in the striatum. To determine the effects on the integrity of the synapse, we purified synaptic membranes, subjected them to quantitative mass spectrometry analysis and found alterations in the complement system, endocytosis and exocytosis pathways. These neuropathological changes coincide with alterations in spontaneous home cage behavior. Taken together, our findings suggest that FBXO7 is crucial for corticostriatal projections and the synaptic integrity of the striatum, and consequently for proper motor control.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:39.288.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Preisinger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-26 18:04:20	ID requested
1	2023-09-18 03:51:45	announced
⏵ 2	2023-11-14 08:55:40	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: brain, LC-MS, mouse,synapse

Judith Stegmüller
contact affiliation	Dept of Neurology University Hospital RWTH Aachen Pauwelsstrasse 30 52074 Aachen Germany
contact email	jstegmueller@ukaachen.de
lab head
Christian Preisinger
contact affiliation	Proteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044119
     1. Label: PRIDE project
     2. Name: Loss of the parkinsonism-associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to anormal motor behavior and synaptic defects