PXD045670

PXD045670 is an original dataset announced via ProteomeXchange.

Title	Zebrafish gabra1 sa43718 allele proteomics
Description	Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the gamma-aminobutyric acid type A receptor (GABAAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have previously been developed to understand the mechanism by which mutations in GABRA1 cause disease, but these models have produced complex and at times incongruent data. Thus, additional model systems are required to validate and substantiate previously published results. We investigated the behavioral patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, a phenotype indicative of seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional alpha sub-units of the GABAAR. Although multiple sub-units were decreased in total expression, larvae continued to respond to pentylenetetrazole (PTZ) indicating that residual GABAARs exist in gabra1 homozygous mutants. Interestingly, shotgun (bottom-up) proteomics of whole brain larval homogenates demonstrated that loss of gabra1 function is associated with abnormal expression of proteins that regulate proton transport, ion homeostasis, vesicle transport, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure like phenotypes with abnormal function of inhibitory synapses.
HostingRepository	PRIDE
AnnounceDate	2025-07-14
AnnouncementXML	Submission_2025-07-13_16:25:01.865.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045670
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nayeli Reyes-Nava
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-25 13:03:07	ID requested
⏵ 1	2025-07-13 16:25:02	announced

Reyes-Nava NG, Paz D, Pinales BE, Perez I, Gil CB, Gonzales AV, Grajeda BI, Estevao IL, Ellis CC, Castro VL, Quintana AM, germline loss of function allele confirms a function for Gabra1 in motility and nervous system development. Differentiation, 138():100790(2024) [pubmed]

10.6019/PXD045670;

10.1016/j.diff.2024.100790;

submitter keyword: sa43718 allele,gabra1, zebrafish, LC-MS/MS

ANITA M. QUINTANA
contact affiliation	Department of Biological Sciences The University of Texas at El Paso US
contact email	aquintana8@utep.edu
lab head
Nayeli Reyes-Nava
contact affiliation	The University of Texas at Austin
contact email	nayeli.reyesnava@austin.utexas.edu
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/2025/07/PXD045670

PRIDE project URI

• PRIDE
  1. PXD045670
     1. Label: PRIDE project
     2. Name: Zebrafish gabra1 sa43718 allele proteomics