High levels of alcohol intake lead to skeletal muscle myopathy and subsequent dysfunction both acutely and chronically. Our previous work has shown that a single dose of alcohol, as well as chronic intake, decreases rates of protein synthesis concurrent with suppression of the mTOR signaling pathway. Although evidence exists for the contribution of other anabolic and catabolic factors (myostatin, inflammation, insulin like growth factor, etc.), to the induction of alcoholic myopathy, no definitive mechanism(s) or pathway(s) has been identified. Therefore, the objective of this work was to identify novel pathways for future therapeutic targeting in the treatment of alcoholic myopathy via an unbiased screen of skeletal muscle specific genes differentially regulated by acute alcohol intoxication. Male, 12 week old, C57BL/6 mice were fasted overnight prior to receiving an intraperitoneal injection of 3g/kg BW alcohol or saline (Control group). The gastrocnemius/plantaris muscle complex was excised 1 hour post alcohol intoxication for isolation of RNA and preparation of cDNA prior to RNA deep sequencing. The data were mapped to the mouse genome (mm10, GRCm38) using TopHat 2 software. Using DESeq2 software, differentially expressed genes were determined based on an FDR‐adjusted p‐value of <0.05. Under these parameters, 48 transcripts were identified in response to acute alcohol intoxication. Using the DAVID Bioinformatics Resource, 8 functional groups were recognized including Collagen, Extracellular matrix, Secreted, Hydroxylation, Cell Adhesion, Cytoplasm, Signal and Glycoprotein. Of the 48 genes, 15 were suppressed by alcohol intoxication including Regulator of Cell Cycle (Rgcc), previously shown to be upregulated in models of skeletal muscle hypertrophy and regrowth; Leiomodin2 (Lmod2) which is important in actin polymerization; and xin actin‐binding repeat containing 1 (Xirp1) which protects actin filaments from depolymerization and may be a marker of muscle damage. The remaining 32 genes were increased by acute alcohol intoxication including EMILIN1 which relies on the inhibition of TGF‐β; Aquaporin7 which is implicated in lipolysis and glycerol efflux via regulation of mTOR‐mediated leptin expression; and MAP3K14, also known as NF‐κB inducible kinase, indicating potential modulation of the NF‐κB pathway by acute alcohol. Of the differentially expressed gene transcripts, several do not appear to have a known functional role in skeletal muscle and will therefore provide novel targets for the further characterization of the effects of alcohol on skeletal muscle.Support or Funding InformationFunds provided by Florida State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.