Overexpression of endothelial β4 integrin has no impact on blood-brain barrier integrity or the pathogenesis of experimental autoimmune encephalomyelitis.

Laminin is a major component of the vascular basement membrane and transgenic mice deficient in astrocyte or pericyte laminin manifest blood-brain barrier (BBB) disruption, implying an important stabilizing role for laminin in BBB integrity. As the laminin receptor α6β4 integrin is strongly induced on CNS blood vessels in the neuroinflammatory animal model experimental autoimmune encephalomyelitis (EAE), and mice deficient in endothelial β4 integrin (β4-EC-KO) display worse EAE, here we tested in a novel transgenic knock-in mouse, whether constitutive overexpression of endothelial β4 integrin (β4-EC-KI) would enhance BBB integrity and reduce EAE development and progression. In immunofluorescent analysis of brain and spinal cord tissue, β4-EC-KI mice showed strong constitutive endothelial β4 integrin expression in all blood vessels, along with upregulation of its α6 integrin subunit partner and the α4 subunit of its physiological ligand, laminin 411. Under disease-free conditions, vascular structure and activation were unchanged in β4-EC-KI mice. In the EAE model, β4-EC-KI mice were no different from wild-type littermate controls in the time of onset, peak clinical score, or progression of EAE. Consistent with this, histopathological analysis revealed no observable differences in levels of BBB disruption, vascular activation, leukocyte infiltration, endothelial tight junction protein expression, or microglial and astrocyte activation. These data demonstrate that while β4-EC-KI mice show strong constitutive expression of endothelial β4 integrin, this had no discernible impact on blood-brain barrier integrity or the pathogenesis of EAE.