It has been shown that even classically-used controls can differ in abundance across different sample types or even by sample handling methods. For example, Gapdh was found to be less stable over time in FFPE breast tumour samples by qRT-PCR whereas it was deemed a suitable reference gene for use in lung tumour FFPE samples. In a proteomic analysis, multiple species of GAPDH were identified within human platelet samples; of these, the most abundant of species was highly variable across both age and sex. This indicates that particular effort must be made when validating loading controls for western blot, as different antibodies may target different species. Exposure to TCDD has been shown to have a dramatically different effect on transcriptomic regulation across various animal models. This has been shown to result from ligand activation of the AHR by TCDD-binding while the degree of toxicity is directly related to the Ahr-genotype within rodents. While studies into the specific transcriptomic changes responsible for overall toxicity are still ongoing, progress has been made in the identification of candidate lists within various animal models, including strains of rats and mice. However, as toxicity likely results from subsequent changes in the proteome, further studies are required to verify which of these candidate genes are Remdesivir GS-5734 concomitantly altered at the protein level. While validation of reference genes for RNA quantitation in various mouse models has been completed, there is no reason to expect similar results to be obtained at the level of the proteome. Here, we have evaluated the protein abundance of 7 reference genes for use in toxico-proteomic analyses of TCDD-induced toxicity within a wide range of mouse models. In particular, we have assessed the effect of TCDD exposure on protein abundance within mouse models of various strains, Ahr-genotype and sex across both a timecourse and dose-response approach. Protein abundance was assessed by quantitative western blot analysis and each candidate’s suitability as a reference control was evaluated using 3 analysis methods: 1) the fold-difference in protein content from basal levels, 2) the NormFinder algorithm, which is an assessment of target stability and 3) the ability of each candidate to reduce instability of the others. As TCDD is known to have a significant impact on transcriptional regulation, and has been shown to affect the proteome, the protein abundance of our candidates was first assessed using biologically similar animals that were treated with either TCDD or corn oil alone. HPRT was identified as the protein least affected by TCDD while EEF1A1 and SDHA showed significant variability across multiple experimental conditions.