Genetic Mouse Models for Nr4a1 and Nr4a3

Nr4a1^–/–, Nr4a1^fl/fl, and Nr4a3^–/– mice were previously described (6 (link), 20 (link), 23 (link)). Nr4a1^fl/fl were previously obtained from Catherine Hedrick (La Jolla Institute for Immunology, La Jolla, California, USA) with permission from Pierre Chambon (University of Strasbourg, Strasbourg, France; ref. 6 (link)). Nr4a1^–/– mice were obtained from The Jackson Laboratory, and this line is used throughout the manuscript exclusively as single germline knockout comparator (23 (link)). Nr4a3^–/– mice were generated in our laboratory as previously described (20 (link)). CD8-cre and mb1-cre were obtained from The Jackson Laboratory (38 (link), 58 (link)). C57BL/6 mice were from The Jackson Laboratory, and CD45.1⁺ BoyJ mice were from Charles River Laboratories. To generate gDKO Nr4a1^–/– Nr4a3^–/– mice, we bred Nr4a3^–/– and Nr4a1^fl/fl mice with germline recombination of the loxp-flanked locus and confirmed loss of exon 2 by genomic DNA PCR and transcript quantitative PCR. All strains were fully backcrossed to C57BL/6 genetic background for at least 6 generations. Mice of both sexes were used for experiments between the ages of 3 and 10 weeks except for BM chimeras as described below.