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Article Dans Une Revue Neurobiology of Disease Année : 2017

Col4a1 mutation generates vascular abnormalities correlated with neuronal damage in a mouse model of HANAC syndrome

Résumé

The HANAC syndrome is caused by mutations in the gene coding for collagen4a1, a major component of blood vessel basement membranes. Ocular symptoms include an increase in blood vessel tortuosity and occasional hemorrhages. To examine how vascular defects can affect neuronal function, we analyzed the retinal phenotype of a HANAC mouse model. Heterozygous mutant mice displayed both a thinning of the basement membrane in retinal blood vessels and in Bruch's membrane resulting in vascular leakage. Homozygous mice had additional vascular changes, including greater vessel coverage and tortuosity. This greater tortuosity was associated to higher expression levels of vascular endothelial growth factor (VEGF). These major changes to the blood vessels were correlated with photoreceptor dysfunction and degeneration. The neuronal damage was associated with reactive gliosis in astrocytes and Müller glial cells, and by the migration of microglial cells into the outer retina. This study illustrates how vascular changes can trigger neuronal degeneration in a new model of HANAC syndrome that can be used to further study dysfunctions of neurovascular coupling.
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Dates et versions

hal-01436672 , version 1 (16-01-2017)

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Alix Trouillet, Henri Lorach, Elisabeth Dubus, Brahim El Mathari, Ivana Ivkovic, et al.. Col4a1 mutation generates vascular abnormalities correlated with neuronal damage in a mouse model of HANAC syndrome. Neurobiology of Disease, 2017, 100, pp.52 - 61. ⟨10.1016/j.nbd.2016.12.014⟩. ⟨hal-01436672⟩
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