TY - JOUR
T1 - Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion
AU - Liedtke, Wolfgang
AU - Edelmann, Winfried
AU - Chiu, Fung Chow
AU - Kucherlapati, Raju
AU - Raine, Cedric S.
PY - 1998/1
Y1 - 1998/1
N2 - Insights into the role of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), have only recently emerged with reports on subtle abnormalities in GFAP-deficient mice, including the documentation of defective long-term maintenance of central nervous system myelination. Here, we extend these observations by examining the astroglial response in GFAP(-/-) mice with autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Clinically, the monophasic disease was more severe in GFAP(-/-) mice than in wild-type littermates despite increased remyelination in the former. More in keeping with the clinical course was the observation of an infiltrative EAE lesion in GFAP(-/-) mice. GFAP(-/-) astrocytes had a reduced cytoarchitectural stability as evidenced by less abundant irregularly spaced hemidesmosomes. The blunt GFAP(-/-) astrocyte processes possessed intermediate filaments consisting mainly of vimentin, though to a lesser degree than in the wild-type. In contrast, in wild-type littermates, GFAP was most abundant and nestin occurred at lower levels. Taken together, the present study introduces the novel concepts that GFAP plays an important role in the control of clinical disease associated with formation of a clearly defined edge to the EAE lesion and that GFAP is operative in the regulation of the intermediate filament components in reactive fibrillary astrogliosis.
AB - Insights into the role of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), have only recently emerged with reports on subtle abnormalities in GFAP-deficient mice, including the documentation of defective long-term maintenance of central nervous system myelination. Here, we extend these observations by examining the astroglial response in GFAP(-/-) mice with autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Clinically, the monophasic disease was more severe in GFAP(-/-) mice than in wild-type littermates despite increased remyelination in the former. More in keeping with the clinical course was the observation of an infiltrative EAE lesion in GFAP(-/-) mice. GFAP(-/-) astrocytes had a reduced cytoarchitectural stability as evidenced by less abundant irregularly spaced hemidesmosomes. The blunt GFAP(-/-) astrocyte processes possessed intermediate filaments consisting mainly of vimentin, though to a lesser degree than in the wild-type. In contrast, in wild-type littermates, GFAP was most abundant and nestin occurred at lower levels. Taken together, the present study introduces the novel concepts that GFAP plays an important role in the control of clinical disease associated with formation of a clearly defined edge to the EAE lesion and that GFAP is operative in the regulation of the intermediate filament components in reactive fibrillary astrogliosis.
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M3 - Article
C2 - 9422542
AN - SCOPUS:0031964424
SN - 0002-9440
VL - 152
SP - 251
EP - 259
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -