For the cuprizone model, adult male mice (ages in Table S1) were fed regular chow mixed with 0.3% cuprizone (Sigma #14690) ad libitum for 5 weeks to induce demyelination as previously described [55 (link)]. For EAE, Lrp1fl/flOlig1Cre and Olig1Cre mice were immunized and scored as previously described [57 (link)].
Tamoxifen (T5648, Sigma) was prepared at 20mg/mL in 0.2μm filtered corn oil (C8267, Sigma) by shaking overnight at 37°C. Lrp1fl/flPdgfraCre-ERt2 adult mice received two IP injections of 200mg/kg Tamoxifen, two days apart. No more than 4mg Tamoxifen per injection was administered to adult mice. Mice were allowed to recover for 4 weeks after the final Tamoxifen injection before EAE immunizations. Lrp1fl/flPdgfraCre-ERt2− and LRP1fl/flPdgfraCre-ERt2+ mice were immunized twice, three weeks apart, due to the immunomodulatory effects of Tamoxifen [6 (link), 31 (link)]. EAE scores for Lrp1fl/flPdgfraCre-ERt2 mice were collected after the second immunization.