PXD018808

PXD018808 is an original dataset announced via ProteomeXchange.

Title	Rescue of oxytocin response and social behavior in a rodent model of autism
Description	One of the most fundamental challenges in developing treatments for autism-spectrum disorders is the heterogeneity of the condition. More than one hundred genetic mutations confer high risk for autism, with each individual mutation accounting for only a small fraction of autism cases. Subsets of risk genes can be grouped into functionally-related pathways, most prominently synaptic proteins, translational regulation, and chromatin modifications. To possibly circumvent this genetic complexity, recent therapeutic strategies have focused on the neuropeptides oxytocin and vasopressin which regulate aspects of social behavior in mammals. However, whether genetic risk factors might predispose to autism due to modification of oxytocinergic signaling remains largely unknown. Here, we report that an autism-associated mutation in the synaptic adhesion molecule neuroligin-3 (Nlgn3) results in impaired oxytocin signaling in dopaminergic neurons and in altered social novelty responses in mice. Surprisingly, loss of Nlgn3 is accompanied by a disruption of translation homeostasis in the ventral tegmental area. Treatment of Nlgn3KO mice with a novel, highly specific, brain-penetrant inhibitor of MAP-kinase interacting kinases resets mRNA translation and restores oxytocin and social novelty responses. Thus, this work identifies an unexpected convergence between the genetic autism risk factor Nlgn3, translational regulation, and oxytocinergic signaling. Focus on such common core plasticity elements might provide a pragmatic approach to reduce the heterogeneity of autism phenotypes. Ultimately, this would allow for mechanism-based stratification of patient populations to increase the success of therapeutic interventions.
HostingRepository	PRIDE
AnnounceDate	2020-04-27
AnnouncementXML	Submission_2020-08-11_22:42:35.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018808
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex; Oxidation; Acetyl; iTRAQ8plex; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-26 14:43:12	ID requested
1	2020-04-27 00:40:21	announced
⏵ 2	2020-08-11 22:42:35	announced	2020-08-12: Updated publication reference for PubMed record(s): 32760004.

H, ö, rnberg H, P, é, rez-Garci E, Schreiner D, Hatstatt-Burkl, é L, Magara F, Baudouin S, Matter A, Nacro K, Pecho-Vrieseling E, Scheiffele P, Rescue of oxytocin response and social behaviour in a mouse model of autism. Nature, 584(7820):252-256(2020) [pubmed]

submitter keyword: Autism, mass spectrometry, PRM

Alexander Schmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018808
     1. Label: PRIDE project
     2. Name: Rescue of oxytocin response and social behavior in a rodent model of autism