| First Author | Kang M | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114123 |
| PubMed ID | 38635399 | Mgi Jnum | J:349798 |
| Mgi Id | MGI:7658785 | Doi | 10.1016/j.celrep.2024.114123 |
| Citation | Kang M, et al. (2024) Oligodendrocyte-derived laminin-gamma1 regulates the blood-brain barrier and CNS myelination in mice. Cell Rep 43(5):114123 |
| abstractText | Although oligodendrocytes (OLs) synthesize laminin-gamma1, the most widely used gamma subunit, its functional significance in the CNS remains unknown. To answer this important question, we generated a conditional knockout mouse line with laminin-gamma1 deficiency in OL lineage cells (gamma1-OKO). gamma1-OKO mice exhibit weakness/paralysis and die by post-natal day 33. Additionally, they develop blood-brain barrier (BBB) disruption in the cortex and striatum. Subsequent studies reveal decreased major facilitator superfamily domain containing 2a expression and increased endothelial caveolae vesicles, but unaltered tight junction protein expression and tight junction ultrastructure, indicating a transcellular, rather than a paracellular, mechanism of BBB breakdown. Furthermore, significantly reduced OL lineage cells, OL precursor cells (OPCs), proliferating OPCs, and mature OLs are observed in gamma1-OKO brains in a region-specific manner. Consistent with this finding, various defects in myelination are detected in gamma1-OKO brains at biochemical and ultrastructural levels. Overall, these results highlight important roles of OL-derived laminin-gamma1 in BBB maintenance and OL biology (proliferation, differentiation, and myelination). |
