1557 Transcriptomic Analysis Demonstrates Good Correlation of a Murine Model of Chronic Dermatitis Induced by Oxazolone with Major Gene Hallmarks of Atopic Dermatitis in Humans

It has been described that repeated topical application of oxazolone in the ears of sensitized mice induces lesions that mimic some features of atopic dermatitis (AD). Previously, we have described the characterization and pharmacological validation of a model of dermatitis induced by 4 challenges of oxazolone (OXA) applied on days 7, 9, 11 and 14 post-sensitization. In the present study we analyze the gene expression/pathway signature induced by OXA, and assess its relevance and correlation with human AD data. Based on these objectives we performed a transcriptome profiling by means of RNA sequencing (HTP pathway high-throughput RNAseq). The experimental set up consisted of 2 groups, naïve and OXA treated with 6 biological replicates per group. For 3' end RNA sequencing, aQuantSeq 3' mRNA-Seq Library Prep Kit was used followed by lllumina single end sequencing with read Length of 75 bp on the NextSeq 500 Sequencing System (lllumina). A strong effect of OXA treatment with respect to untreated ear in sensitized animals and with respect to vehicle treated animals in not sensitized animals was detected. To assess the transferability of our model to human, we calculated a similarity score (Pearson correlation) between the fold changes from the RNA-seq of our model with fold changes from different previously published human studies in AD and psoriasis (PS). As expected, our model was reflecting well the transcriptomic impact between lesional and non-lesional samples in both studies. Importantly, we observed a significantly higher similarity in these fold changes for AD samples than for PS. Overall, our results show that this model replicates relevant transcriptomic human AD features showing better correlation with AD than with other skin autoimmune conditions such as PS, making it suitable for screening and molecule profiling purposes.