The low-density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane
receptor, mediating endocytosis and activating intracellular signaling cascades. LRP1 is highly
expressed in the central nervous system (CNS), especially in oligodendrocyte precursor cells
(OPCs). Previous studies have suggested LRP1 as a regulator in early oligodendrocyte development,
repair of chemically induced white matter lesions, and cholesterol homeostasis. To circumvent
embryonic lethality observed in the case of global LRP1 deletion, we generated a new inducible
conditional knockout (KO) mouse model, which enabled an NG2-restricted LRP1 deficiency
(NG2-CreERT2ct2/wtxR26eGFPflox/floxxLRP1flox/flox). When characterizing our triple transgenic mouse
model, we noticed a substantial and progressive loss of recombined LRP1-deficient cells in the
oligodendrocyte lineage. On the other hand, we found comparable distributions and fractions of
oligodendroglia within the Corpus callosum of the KO and control animals, indicating a compensation
of these deficits. An initial study on experimental autoimmune encephalomyelitis (EAE) was
performed in triple transgenic and control mice and the cell biology of oligodendrocytes obtained
from the animals was studied in an in vitro myelination assay. Differences could be observed in these
assays, which, however, did not achieve statistical significance, presumably because the majority
of recombined LRP1-deficient cells has been replaced by non-recombined cells. Thus, the analysis
of the role of LRP1 in EAE will require the induction of acute recombination in the context of the
disease process. As LRP1 is necessary for the survival of OPCs in vivo, we assume that it will play an
important role in myelin repair
