Abnormal Reaction to Central Nervous System Injury in Mice Lacking Glial Fibrillary Acidic Protein and Vimentin

doi:10.1083/jcb.145.3.503

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J. Cell Biol., Volume 145, Number 3, May 3, 1999 503-514

Abnormal Reaction to Central Nervous System Injury in Mice Lacking Glial Fibrillary Acidic Protein and Vimentin

Milos Pekny,^* Clas B. Johansson,^§ Camilla Eliasson,^* Josefina Stakeberg,^* Åsa Wallén,^¶ Thomas Perlmann,^¶ Urban Lendahl,^§ Christer Betsholtz,^* Claes-Henric Berthold, and Jonas Frisén^§

^* Department of Medical Biochemistry and Department of Anatomy and Cell Biology, Gothenburg University, SE-405 30 Gothenburg, Sweden; and ^§ Department of Cell and Molecular Biology, Medical Nobel Institute, Department of Neuroscience, Karolinska Institute and ^¶ Ludwig Institute for Cancer Research, Stockholm Branch, SE-17177 Stockholm, Sweden

In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediatefilament (IF) proteins glial fibrillary acidic protein (GFAP),vimentin, and nestin. We have shown that astrocytes in mice deficientfor both GFAP and vimentin (GFAP $-$ / $-$ vim $-$ / $-$ ) cannot form IFs evenwhen nestin is expressed and are thus devoid of IFs in their reactivestate. Here, we have studied the reaction to injury in the centralnervous system in GFAP $-$ / $-$ , vimentin $-$ / $-$ , or GFAP $-$ / $-$ vim $-$ / $-$ mice.Glial scar formation appeared normal after spinal cord or brainlesions in GFAP $-$ / $-$ or vimentin $-$ / $-$ mice, but was impaired in GFAP $-$ / $-$ vim $-$ / $-$ mice that developed less dense scars frequently accompanied bybleeding. These results show that GFAP and vimentin are requiredfor proper glial scar formation in the injured central nervoussystem and that some degree of functional overlap exists betweenthese IFproteins.

Key words: GFAP; nestin; injury; astrocyte; blood vessel

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