Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin.
In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP-/-vim-/-) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP-/-, vimentin-/-, or GFAP-/-vim-/- mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.
Pekny
M
M
Department of Medical Biochemistry, Gothenburg University, SE-405 30 Gothenburg, Sweden. milos.pekny@medkem.gu.se
Johansson
C B
CB
Eliasson
C
C
Stakeberg
J
J
Wallén
A
A
Perlmann
T
T
Lendahl
U
U
Betsholtz
C
C
Berthold
C H
CH
Frisén
J
J
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002921:Cicatrix / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004805:Ependyma / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins; D064231:Nestin; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism; D014951:Wounds, Stab / Q000235:genetics / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D014746:Vimentin