Intermediate filaments are general constituents of the cytoskeleton. The fu
nction of these structures and the requirement for different types of inter
mediate filament proteins by individual cells are only partly understood. H
ere we have addressed the role of specific intermediate filament protein pa
rtnerships in the formation of intermediate filaments in astrocytes. Astroc
ytes may express three types of intermediate filament proteins: glial fibri
llary acidic protein (GFAP), vimentin, and nestin. me used mice with target
ed mutations in the GFAP or vimentin genes, or both, to study the impact of
loss of either or both of these proteins on intermediate filament formatio
n in cultured astrocytes and in normal or reactive astrocytes in vivo. We r
eport that nestin cannot form intermediate filaments on its own, that vimen
tin may form intermediate filaments with either nestin or GFAP as obligator
y partners, and that GFAP is the only intermediate filament protein of the
three that may form filaments on its own. However, such filaments show abno
rmal organization. Aberrant intermediate filament formation is linked to di
seases affecting epithelial, neuronal, and muscle cells. Here we present mo
dels by which the normal and pathogenic functions of intermediate filaments
may be elucidated in astrocytes.