PXD052868-1

PXD052868 is an original dataset announced via ProteomeXchange.

Title	Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties
Description	Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), ADHD, learning difficulties and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional Astn2 knockout (KO and cKO, respectively) mouse lines. Astn2 KO mice exhibited strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity, and repetitive behaviors, altered behavior in the three-chamber test, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors were also prominent in Astn2 cKO animals but they did not show altered behavior in the three-chamber test. By Golgi staining, Astn2 KO PCs had region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of Astn2 KO cerebellum revealed a marked upregulation of ASTN2 family member, ASTN1, a neuron-glial adhesion protein. Immunohistochemistry and electron microscopy demonstrated a significant increase in Bergmann glia volume in the molecular layer of Astn2 KO animals. Electrophysiological experiments indicated a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents (IPSCs) in the Astn2 KO animals, suggesting that pre- and postsynaptic components of synaptic transmission were altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.
HostingRepository	PRIDE
AnnounceDate	2024-07-30
AnnouncementXML	Submission_2024-07-30_08:21:35.458.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	henrik molina
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-05 12:25:51	ID requested
⏵ 1	2024-07-30 08:21:35	announced
2	2024-10-22 06:51:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: ASTN2, Purkinje cell, neurodevelopmental disorder, Cerebellum,Autism Spectrum Disorder

Mary E. Hatten
contact affiliation	The Rockefeller University
contact email	hatten@rockefeller.edu
lab head
henrik molina
contact affiliation	THE ROCKEFELLER UNIVERSITY
contact email	henrik.molina@gmail.com
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/2024/07/PXD052868

PRIDE project URI

• PRIDE
  1. PXD052868
     1. Label: PRIDE project
     2. Name: Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties