S27 Adam33 knockout mice have an altered metabolic transcriptional profile in response to house dust mite when compared to wild type mice

Rationale ADAM33 is an asthma susceptibility gene that plays a role in both airway remodelling and susceptibility to allergic airways disease. To study the role of ADAM33 in asthma we have exposed an Adam33 Knockout (KO) mouse to a house dust mite (HDM) sensitisation and challenge protocol. We have found that these mice exhibit less remodelling, bronchial hyperresponsiveness (BHR) and eosinophilic inflammation than wild type (WT) mice (ER Davies et al., JCI-Insight 2016), however the mechanisms which contribute to this protective phenotype are not well understood. Methods To study how the response to HDM is altered by loss of Adam33 we challenged WT and KO mice with HDM or saline and took whole lung RNA samples for next generation RNA sequencing (RNAseq). Gene set enrichment analysis was used to identify pathways and gene ontology terms associated with the differential response to HDM between KO and WT mice. Results Control WT and KO mice were found to have very similar gene expression profiles at baseline (5 differentially expressed genes, including Adam33, FDR p Discussion The alteration in the pulmonary metabolic gene signature may underpin a shift in immune cell activation and/or modification of smooth muscle energy expenditure during airway contraction. These changes may explain why the KO mouse is protected from both allergic responses and BHR. Further work will aim to identify the source of the different metabolic behaviour at a cellular level and to assess oxidative stress in lungs of normal and Adam33 KO mice.