Expression analysis of WT or Card14E138A ears 5 days and 1 month after injecton of tamoxifen

The inducible nature of our knock-in mouse strain allowed us to determine the immediate effects of dysregulated CARD14 signalling and compare them to the long term effects of its expression. CARD14E138A-induced skin inflammation and systemic disease were independent of adaptive immune cells, substantially reduced by antibody blocking of TNF and induced by CARD14E138A signaling only in keratinocytes. To investigate how psoriasis-associated mutations in CARD14 induce psoriasis, we have generated a Card14LSL-E138A knock-in mouse that allows conditional expression of Card14E138A from the endogenous mouse Card14 locus via tamoxifen activation of CreERT2. The highly penetrant CARD14E138A psoriasis-associated mutation was first identified in a child suffering from GPP and induces CARD14 to constitutively activate NF-kB. The new Card14LSL-E138A strain allowed the immediate and chronic effects of CARD14E138A signaling to be studied, as well as the cell types involved.