Endothelial SOCS3-Knockout Mouse Model

Endothelial specific, tamoxifen-inducible SOCS3-knockout mice were generated by breeding B6.Tg(Cdh5-cre/ERT2)1Rha (Cdh5-CreER^T2 endothelial driver) mice (91 (link)) (a gift from Kevin Pumiglia, Albany Medical College, Albany, New York, USA) with B6.Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze} (ROSA26-tdTomato reporter) (92 (link)) and B6;129S4-Socs3^tm1Ayos/J (SOCS3^fl/fl conditional knockout) (93 (link)) mice (The Jackson Laboratory). Mice were backcrossed to a full C57BL6/J background by breeding to C57BL6/J mice (The Jackson Laboratory) for at least 10 generations. Knockouts and heterozygous and control littermates were obtained by crossing Cre⁺ tdTomato⁺ SOCS3^fl/+ mice. Genotypes and sex were confirmed by PCR genotyping (Supplemental Table 4). All mice received tamoxifen (2 mg tamoxifen in 100 μL via intraperitoneal [IP] injection) at 6–9 weeks old for 5 consecutive days. Deletion of the target gene after tamoxifen was confirmed by tail digestion and PCR. All the experiments were conducted between 2 and 3 weeks after the end of tamoxifen treatment.