Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice.

[alexander disease]

Alexander disease is a fatal leukoencephalopathy caused by dominantly-acting coding mutations in GFAP . Previous work has also implicated elevations in absolute levels of GFAP as central to the pathogenesis of the disease . However , identification of the critical astrocyte functions that are compromised by mis-expression of GFAP has not yet been possible . To provide new tools for investigating the nature of astrocyte dysfunction in Alexander disease , we have established primary astrocyte cultures from two mouse models of Alexander disease , a transgenic that over-expresses wild type human GFAP , and a knock-in at the endogenous mouse locus that mimics a common Alexander disease mutation . We find that mutant GFAP , as well as excess wild type GFAP , promotes formation of cytoplasmic inclusions , disrupts the cytoskeleton , decreases cell proliferation , increases cell death , reduces proteasomal function , and compromises astrocyte resistance to stress .

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Diseases presenting "also implicated elevations in absolute levels" symptom

alexander disease

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