Next, the function of SETDB1 was assessed in the remyelination process following lysolecithin (LPC)-induced demyelination using Setdb1Flox/Flox; Pdgfra-CreER mice (Pdgfra-CreER; Setdb1F/F) in which SETDB1 was ablated in OPCs upon tamoxifen administration. Local injection of LPC in the white matter induces rapid myelin breakdown followed by regeneration29. There are an OPC proliferation and recruitment phase at 7-day post-lesion (Dpl) and then a remyelinating phase at 14 Dpl. LPC was injected into the corpus callosum of Pdgfra-CreER; Setdb1F/F mice or control mice (Pdgfra-CreER; Setdb1F/+) P60, followed by tamoxifen administration for consecutive 3 days (Fig. 4a). Immunostaining revealed successful creation of lesions (Supplementary Fig. 5a) and that the injured areas were similar between control and mutant mice (Supplementary Fig. 5b). The remyelination in control mice were almost completed indicated by the recurrence of MBP; but significant smaller MBP+ areas were observed in the mutant mice (Fig. 4b). Expression of the myelin-associated genes such as Plp1 (Fig. 4c, d) and Mbp (Supplementary Fig. 5c, d) were decreased in the lesion areas of mutant mice. Ultrastructural analyses on the lesions again revealed markedly lower percentage
