B6n cg tg krt14 cre 1amc j

All experiments were performed on age-matched (from 8 to 12 weeks of age) female mice. Wild type C57Bl/6 mice were purchased from Envigo. Mapk8^fl/fl mice (C57BL/6 background) were previously described (9 (link)) and kindly provided by Thomas Wunderlich and Jens Brüning, Institute for Genetics, University of Cologne. B6.C-Tg(Pgk1-cre)1Lni/CrsJ (stock 020811), B6.129P2-Lyz2tm1(cre)Ifo/J (stock 004781), B6N.Cg-Tg(KRT14-cre)1Amc/J (stock 018964) and B6.Cg-Tg(Itgax-cre)1-1Reiz/J (stock 008068) mice were obtained from the Jackson Lab. Littermates were used as controls in all experiments. All mice were bred and maintained in a conventional animal facility.

All animal studies were conducted under approved protocols from Institutional Animal Care and Use Committee. Rora^{tm1a(EUCOMM)Wtsi} (Rora^tm1a/+) embryonic stem cells were obtained from INFRAFRONTIER/EMMA (European Mouse Mutant Archive, Munich, Germany) and subjected to in vitro injection into the C57BL/6 female mice to generate the Rora^tm1a/+ mice (performed by Animal Models of Biotechnology at the University of Wisconsin, Madison, WI, USA). A male Rora^tm1a/+ mouse was crossed with a female Sox2 (SRY-box containing gene 2)-Cre transgenic mouse (B6.Cg-Edil3^{Tg(Sox2-cre)1Amc}/J; The Jackson Laboratory, Bar Harbor, ME, USA) [69 (link)] to generate the Rora^tm1b/+ strain (Rora^LacZΔ/+), which contains a LacZ-cassette upstream the deleted Rora exon 3 (Figure 1A). To generate the Rora^tm1c/+ (Rora^flox/+) mice, the Rora^tm1a/+ mice were crossed with ACTB-FLPe transgenic mice (B6.Cg-Tg(ACTFLPe)9205Dym/J; The Jackson Laboratory) to delete the FRT-flanked section. The Rora^flox/+; FLP mice were backcrossed with wildtype C57BL/6 mice to remove FLP [39 (link)]. The Rora^LacZΔ/EKO mice were generated by crossing the Rora^flox/flox strain with the Rora^LacZΔ/+;K14-Cre strain (B6N.Cg-Tg(KRT14-cre)1Amc/J, The Jackson Laboratory). The Rora^EKO mice were generated by crossing the Rora^flox/flox strain with the K14-Cre strain.

Il1rl2floxed (Il36r^fl) transgenic mice were generated on a C57Bl/6 background by Cyagen Biosciences (see Fig S1A for outline of strategy). Exon 4 was selected as the conditional KO region and deletion of this exon was predicted to result in loss of function of the mouse Il1rl2 gene. Mouse genomic fragments containing homology arms and conditional KO region were amplified from the BAC clone by using high-fidelity Taq and were sequentially assembled into a targeting vector together with recombination sites and selection markers (Fig S1A). After confirming correctly targeted ES clones via Southern blotting, the clones were selected for blastocyst microinjection, followed by chimera production. Founders were confirmed as germ line–transmitted via crossbreeding with wild-type C57Bl/6 mice. Mutant mice received were heterozygous for the transgene. Heterozygous mice were mated to obtain homozygous in house (Fig S1B). Transgenic mice were identified by DNA extraction of ear tissue and amplification by PCR of the transgene. The K14^Cre mice (B6N.Cg-Tg(KRT14-cre)1Amc/J) were obtained from Jackson Laboratories (Strain 004782). In these mice, the expression of Cre recombinase in keratinocytes is controlled by a human keratin 14 promoter. Il36rflox mice were mated with K14^Cre mice to generate K14^Cre+Il36r^fl/fl (Il36rΔK).