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

Abstract

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.

Tumorigenesis in transgenic mice in which the SV40 T antigen is driven by the brain-specific FGF1 promoter

“…For example, vimentin is expressed in progenitor cells that retain the plasticity to di erentiate into cells of neuronal or glial lineage; it is replaced by synaptophysin and neuron-speci®c enolase in mature neurons, and by GFAP in astrocytes (Pekny et al, 1999). Three di erent intermediate ®laments, nestin, vimentin, and GFAP, are found in astrocytes and their precursors.…”

Prefractionation of Cerebrospinal Fluid to Enhance Glycoprotein Concentration Prior to Structural Determination with FT−ICR Mass Spectrometry

“…Mouse transgenic models were developed to assess the role of reactive gliosis in CNS pathologies and regeneration, in which two astrocyte intermediate filament proteins, glial fibrillary acidic protein (GFAP) and vimentin (Vim) were genetically removed by gene targeting in vivo (104). GFAP -/-Vim -/-mice show slower wound healing and reduced glial scaring after brain or spinal cord trauma (105). The Pekny group and others have previously reported improved regeneration in GFAP -/-Vim -/-mice, specifically axonal regeneration (106), (107), survival and integration of neuronal grafts in the retina (108) or improved synaptic regeneration in the denervated dentate gyrus of the hippocampus (109), for a review see (102).…”

Worms reveal essential functions for intermediate filaments

“…Finally, in the case of two other Type III IF gene knockouts, no obvious phenotypes were initially discovered, and mice negative for vimentin (6) and glial fibrillary acidic protein (GFAP; ref. 7 and references therein) survived to reproductive age. However, more recent work has shown more subtle phenotypes in these mice, such as defects in wound healing in the vimentin knockouts (8), and in the response of astrocytes to traumatic brain injury in the GFAP null animals (7).…”

“…7 and references therein) survived to reproductive age. However, more recent work has shown more subtle phenotypes in these mice, such as defects in wound healing in the vimentin knockouts (8), and in the response of astrocytes to traumatic brain injury in the GFAP null animals (7). From these studies, it is obvious that analyses of IF function in mouse models are extremely complex and difficult to interpret.…”