Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.

ABSTRACT: 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 By

SUBMITTER: Lynch WB 

PROVIDER: S-EPMC11383981 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature