PXD056873

PXD056873 is an original dataset announced via ProteomeXchange.

Title	Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior
Description	Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified Zhx2 as a candidate gene underlying increased brain concentration of the oxycodone (OXY) metabolite oxymorphone (OMOR) in BALB/cJ (J) versus BALB/cByJ (By) females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors. We tested this hypothesis by restoring the Zhx2 loss-of-function in Js (MVKO) and modeling the loss-of-function variant through knocking out the Zhx2 coding exon (E3KO) in Bys and assessing brain OXY metabolite levels and behavior. Consistent with our hypothesis, Zhx2 E3KO females showed an increase in brain OMOR levels and OXY-induced locomotor activity. However, contrary to our hypothesis, state-dependent expression of OXY-CPP was decreased in E3KO females and increased in E3KO males. We also overexpressed Zhx2 in the livers and brains of Js and observed Zhx2 overexpression in select brain regions that was associated with reduced OXY state-dependent learning. Integrative transcriptomic and proteomic analysis of E3KO mice identified astrocyte function, cell adhesion, extracellular matrix properties, and endothelial cell functions as pathways influencing brain OXY metabolite concentration and behavior. These results support Zhx2 as a quantitative trait gene underlying brain OMOR concentration that is associated with changes in OXY behavior and implicate potential quantitative trait mechanisms that together inform our overall understanding of Zhx2 in brain function.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_17:25:34.645.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056873
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stanley Goldstein
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 13:45:15	ID requested
⏵ 1	2026-03-29 17:25:36	announced

10.1016/j.jpet.2025.103557;

Lynch WB, Miracle SA, Goldstein SI, Beierle JA, Bhandari R, Gerhardt ET, Farnan A, Nguyen BM, Wingfield KK, Kazerani I, Saavedra GA, Averin O, Baskin BM, Ferris MT, Reilly CA, Emili A, Bryant CD, Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior. bioRxiv, ():(2024) [pubmed]

Lynch WB, Miracle SA, Goldstein SI, Beierle JA, Bhandari R, Gerhardt ET, Farnan A, Nguyen BM, Wingfield KK, Kazerani I, Saavedra GA, Averin O, Baskin BM, Ferris MT, Reilly CA, Emili A, Bryant CD, Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior. J Pharmacol Exp Ther, 392(5):103557(2025) [pubmed]

10.6019/PXD056873;

10.1101/2024.08.30.610534;

submitter keyword: Multiomics,Mouse, Brain

Camron Bryant
contact affiliation	Professor and Principal Investigator Laboratory of Addicition Genetics Bouve College of Health Sciences Northeastern University Boston, Massachusetts, USA
contact email	c.bryant@northeastern.edu
lab head
Stanley Goldstein
contact affiliation	Boston University
contact email	stangold@bu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056873
     1. Label: PRIDE project
     2. Name: Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior