Abstract
It is now well established that the glial fibrillary acidic protein (GFAP) is the principal 8–9 nm intermediate filament in mature astrocytes of the central nervous system (CNS). Over a decade ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized (Raine, 135). As a member of the cytoskeletal protein family, GFAP is thought to be important in modulating astrocyte motility and shape by providing structural stability to astrocytic processes. In the CNS of higher vertebrates, following injury, either as a result of trauma, disease, genetic disorders, or chemical insult, astrocytes become reactive and respond in a typical manner, termed astrogliosis. Astrogliosis is characterized by rapid synthesis of GFAP and is demonstrated by increase in protein content or by immunostaining with GFAP antibody. In addition to the major application of GFAP antisera for routine use in astrocyte identification in the CNS, the molecular cloning of the mouse gene in 1985 has opened a new and rich realm for GFAP studies. These include antisense, null mice, and numerous promoter studies. Studies showing that mice lacking GFAP are hypersensitive to cervical spinal cord injury caused by sudden acceleration of the head have provided more direct evidence for a structural role of GFAP. While the structural function of GFAP has become more acceptable, the use of GFAP antibodies and promoters continue to be valuable in studying CNS injury, disease, and development.
REFERENCES
Eng, L. F., Gerstl, B., and Vanderhaeghen, J. J. 1970. A study of proteins in old multiple sclerosis plaques. Trans. Am. Soc. Neurochem. 1:42.
Eng, L. F., Vanderhaeghen, J. J., Bignami, A., and Gerstl, B. 1971. An acidic protein isolated from fibrous astrocytes 1971. Brain Res. 28:351-354.
Uyeda, C. T., Eng, L. F., and Bignami, A. 1972. Immunological study of the glial fibrillary acidic protein. Brain Res. 37: 81-89.
Bignami, A., Eng, L. F., Dahl, D., and Uyeda, C. T. 1972. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 43:429-435.
Eng, L. F., Bond, P., and Gerstl, B. 1971. Isolation of myelin proteins from disc acrylamide gels electrophoresed in phenolformic acid-water. Neurobiol. 1:58-63.
Malloch, G. D. A., Clark, J. B., and Burnet, F. R. 1987. Glial fibrillary acidic protein in the cytoskeletal and soluble protein fractions of the developing rat brain. J. Neurochem. 48: 299-306.
Chiu, F.-C. and Goldman, J. E. 1984. Synthesis and turnover of cytoskeletal proteins in cultured astrocytes. J. Neurochem. 42:166-174.
Aquino, D. A., Chiu, F. C., Brosnan, C. F., and Norton, W. T. 1988. Glial fibrillary acidic protein increases in the spinal cord of Lewis rats with acute experimental autoimmune encephalitis. J. Neurochem. 51:1085-1096.
Bigbee, J. W., Bigner, D. D., Pegram, C., and Eng, L. F. 1983. Study of glial fibrillary acidic protein in a human glioma cell line grown in culture and as a solid tumor. J. Neurochem. 40: 460-467.
DeArmond, S. J., Fajardo, M., Naughton, S. A., and Eng, L. F. 1983. Degradation of glial fibrillary acidic protein by a calcium dependent proteinase: an electroblot study. Brain Res. 262:275-282.
Nelson, W. J. and Traub, P. 1983. Proteolysis of vimentin and desmin by the Ca2+-activated proteinase specific for these intermediate filament proteins. Mol. Cell Biol. 3:1146-1156.
Schlaepfer, W. W. and Zimmerman, V.-J. P. 1981. Calcium-mediated breakdown of glial filaments and neurofilaments in rat optic nerve and spinal cord. Neurochem. Res. 6:243-255.
Johnson, L. and Sinex, F. M. 1974. On the relationship of brain filaments to microtubules. J. Neurochem. 22:321-326.
Dahl, D. 1976. Glial fibrillary acidic protein from bovine and rat brain degradation in tissues and homogenates. Biochem. Biophys. Acta 420:142-154.
Dahl, D. 1976. Isolation and initial characterization of glial fibrillary acidic protein from chicken, turtle, frog, and fish central nervous system. Biochim. Biophys. Acta 446:41-50.
Dahl, D. and Bignami, A. 1976. Immunogenic properties of the glial fibrillary acidic protein. Brain Res. 116:150-157.
Chan, P. H., Huston, J. S., Moo-Penn, W. F., Dahl, D., and Bignami, A. 1977. Biochemical studies related to CNS regeneration: Isolation and partial characterization of urea-soluble gliofibrillary acidic protein from bovine brain. Proc. Annu. Maine Biomed. Symp. 2:496-524.
Wisniewski, H., Shelanski, M. L., and Terry, R. D. 1968. Effects of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells. J. Cell Biol. 38:224-229.
Wisniewski, H., Terry, R. C., and Hirano, A. 1971. Neurofibrillary pathology. J. Neuropathol. Exp. Neurol., 29:173-181.
Gaskin, F. and Shelanski, M. L. 1976. Microtubules and intermediate filaments. Essays Biochem. 12:115-146.
Iqbal, K., Grundke-Iqbal, I., Wisniewski, H. M., and Terry, R. D. 1977. On neurofilament and neurotubule proteins from human autopsy tissue. J. Neurochem. 29:417-424.
Dahl, D. and Bignami, A. 1977. Preparation of antisera to neurofilament protein from chicken brain and human sciatic nerve. J. Comp. Neurol. 176:645-657.
Dahl, D. and Bignami, A. 1976. Isolation from peripheral nerve of a protein similar to the glial fibrillary acidic protein. FEBS Lett. 66:281-284.
Yen, S. H., Dahl, D., Schachner, M., and Shelanski, M. L. 1976. Biochemistry of the filaments of brain. Proc. Natl. Acad. Sci. USA 73:529-533.
Davison, P. F. 1975. Neuronal fibrillar proteins and axoplasmic transport. Brain Res. 100:73-80.
Davison, P. F. and Hong, B. S. 1977. Filaments in nervous tissue and muscle cells. Int. Meet. Int. Soc. Neurochem. 6th, Abstracts, p. 106.
Day, W. A. 1977. Solubilization of neurofilaments from central nervous system myelinated nerve. J. Ultrastruct. Res. 60:362-372.
Goldman, J. E., Schaumburg, H. H., and Norton, W. T. 1978. Isolation and characterization of glial filaments and neurofilaments from human brain. Similarity of the major protein components. J. Cell Biol. 78:426-444.
Lee, V., Yen, S. H., and Shelanski, M. L. 1977. Biochemical correlates of astrocytic proliferation in the mutant Staggerer mouse. Brain Res. 128:389-392.
DeVries, G. H., Eng, L. F., Lewis, D. H., and Hadfield, M. G. 1976. The protein composition of bovine myelin-free axons. Biochim. Biophys. Acta 439:133-145.
Eng, L. F., DeVries, G. H., Lewis, D. L., and Bigbee, J. W. 1976. Specific antibody to the major 47,000 MW protein fraction of bovine myelin-free axons. Fed. Proc. Fed. Am. Soc. Exp. Biol. 35:1766.
Bignami, A. and Dahl, D. 1977. Specificity of the glial fibrillary acidic protein for astroglia. J. Histochem. Cytochem. 25:466-469.
Liem, R. K. H., Yen, S. H., Salomon, G. D., and Shelanski, M. L. 1978. Intermediate filaments in nervous tissue. J. Cell Biol. 79:637-645.
Schachner, M., Smith, C., and Schoonmaker, G. 1978. Immunological distinction between neurofilament and glial fibrillary acidic protein by mouse antisera and their immunohistological characterization. Dev. Neurosci. 1:1-14.
Schlaepfer, W. W., Freeman, L. A., and Eng, L. F. 1979. Studies of human and bovine spinal nerve roots and the evagination of CNS tissues into the nerve root entry zone. Brain Res. 177: 219-229.
Chiu, F.-C., Korey, B., and Norton, W. T. 1980. Intermediate filaments from bovine, rat and human CNS. Mapping analysis of the major proteins. J. Neurochem. 34:1149-1159.
Eng, L. F. 1985. Glial fibrillary acidic protein: The major protein of glial intermediate filaments in differentiated astrocytes. J. Neuroimmunol. 8:203-214.
McLendon, R. E. and Bigner, D. D. 1994. Immunohistochemistry of the glial fibrillary acidic protein: Basic and applied considerations. Brain Pathol. 4:221-228.
Eng, L. F. and Ghirnikar, R. S. 1994. GFAP and astrogliosis. Brain Pathol. 4:229-237.
Inagaki, M., Nakamura, Y., Masatoshi, T., Nushimura, T., and Inagaki, N. 1994. Glial fibrillary acidic protein: Dynamic property and regulation by phosphorylation. Brain Pathol. 4:239-243.
Brenner, M. 1994. Structure and transcriptional regulation of the GFAP gene. Brain Pathol. 4:245-257.
Laping, N. J., Teter, B., Nichols, N. R., Rozovsky, I., and Finch, C. E. 1994. Glial fibrillary acidic protein: Regulation by hormones, cytokines, and growth factors. Brain Pathol. 4:259-275.
Brenner, M. and Messing, A. 1996. GFAP Transgenic Mice. Methods: A companion to methods in enzymology. 10:351-364.
Eng, L. F. and Lee, Y. L. 1995. Intermediate filaments in astrocytes. In Neuroglia, pp. 650-667. H. Kettermann and B. R. Ransom, eds. Oxford University Press.
Eng, L. F. and Lee, Y. L. 1998. Glial response to injury, disease, and aging. In astrocytes in brain aging and neurodegeneration, pp. 71-89. H. M. Schipper, ed. R. G. Landes Co., Georgetown, TX.
Eddleston, M. and Mucke, L. 1993. Molecular profile of reactive astrocytes; implications for their role in neurologic diseases. Neurosci. 54:15-36.
Nichols, N. R., Day, J. R., Laping, N. J., Johnson, S. A., and Finch, C. E. 1993. GFAP mRNA increases with age in rat and human brain. Neurobiol. Aging 14:421-429.
Hallpike, J. F., Adams, C. W. M., and Tourtellotte, W. W. 1983. Multiple Sclerosis. Pathology, diagnosis and management, Williams & Wilkins: Baltimore.
Schaumburg, H. H., Powers, J. M., Raine, C. S., Suzuki, K., and Richardson, E. P. 1975. Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Arch Neurol. 33:577-591.
Goldman, J. E., Schaumburg, H. H., and Norton, W. T. 1978. Isolation and characterization of glial filaments from human brain. J. Cell Biol. 78:426-440.
Eng, L. F., Lee, Y. L., Kwan, H., Brenner, M., and Messing, A. 1998. Astrocytes cultured from transgenic mice carrying the added human glial fibrillary acidic protein gene contain Rosenthal fibers. J. Neurosci. Res. 53:353-360.
Calne, D. B. 1994. Neurodegenerative Diseases, ed. WB Saunders, Philadelphia.
Duffy, P. E., Rapoport, M., and Graf, L. 1980. Glial fibrillary acidic protein and Alzheimer-type senile dementia. Neurol. 30:778-782.
Schechter, R., Yen, S.-H. C., and Terry, R. D. 1981. Fibrous astrocytes in senile dementia of the Alzheimer type. J. Neuropathol. Exp. Neurol. 40:95-101.
Mancardi, G. L., Liwnicz, B. H., and Mandybur, T. I. 1983. Fibrous astrocytes in Alzheimer's disease and senile dementia of Alzheimer's type. An immunohistochemical and ultrastructural study. Acta Neuropathol. (Berl.) 61:76-80.
Beach, T. B. and McGeer, E. G. 1988. Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer disease visual cortex. Brain Res. 463:357-361.
Beach, T. G., Walker, R., and McGeer, E. G. 1989. Patterns of gliosis in Alzheimer's disease and aging cerebrum. Glia 2: 420-436.
Mandybur, T. I. 1989. Cerebral amyloid angiopathy and astrocytic gliosis in Alzheimer's disease. Acta Neuropathol. (Berl.) 78:329-331.
Vijayan, V., Geddes, J. W., Anderson, K. J., Chang-Chui, H., Ellis, W. G., and Cotman, C. W. 1991. Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation. Exp. Neurol. 112:72-78.
Joachim, C. L., Morris, J. H., and Selkoe, D. J. 1989. Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am. J. Pathol. 135:309-319.
Rozemuller, J. M., Eikelenboom, P., Stam, F. C., Beyreuther, K., and Masters, C. L. 1989. A4 protein in Alzheimer's disease: primary and secondary cellular events in extracellular amyloid deposition. J. Neuropathol. Exp. Neurol. 48:674-691.
Suenaga, T., Hirano, A., Llena, J. F., Ksiezak-Reding, H., Yen, S. H., and Dickson, D. W. 1990. Modified immunocytochemical studies in cerebellar plaques in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 49:31-40.
Malamud, N. 1972. Neuropathology of organic brain syndromes associated with aging. In: Aging and the Brain, Gaitz, C. (ed.), pages 63-87, Plenum: New York.
Burger, P. C. and Vogel, S. 1973. The development of pathologic changes of Alzheimer's disease and senile dementia in patients with Down's syndrome. Am. J. Pathol. 73:457-476.
Mann, D. M. A. 1988. The pathological association between Down's syndrome and Alzheimer's disease. Mech. Aging Dev. 43:99-136.
Murphy, G. M., Eng, L. F., Ellis, W. G., Perry, G., Meissner, L. C., and Tinklenberg, J. R. 1990. Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease. Brain Res. 537:102-108.
Murphy, G. M., Jr., Murphy, E., Greenberg, B. D., Cordell, B., Eng, L. F., Elis, W. G., Forno, L. S., Salamat, S., Gonzalez-DeWitt, P. A., Lowry, D. E., and Tinklenberg, J. R. 1991. Alzheimer's disease: beta-amyloid precursor protein expression in plaques varies among cytoarchitectonic areas of the medial temporal lobe. Neurosci. Lett. 131:100-104.
Murphy, G. M., Jr., Ellis, W. G., Lee, Y. L., Stultz, K. E., Shrivastava, R., Tinklenberg, J. R., and Eng, L. F. 1992. Astrocytic gliosis in the amygdala in Down's syndrome and Alzheimer's disease. In: Progress in Brain Research, Vol. 94, Yu, A. C. H., Hertz, L., Norenberg, M. D., Sykova, E., Waxman, S. G. (eds.), Chapter 40, pp. 475-483, Elsevier Science Publishers B.V. Amsterdam.
Michetti, F., Larocca, L. M., Rinelli, A., and Lauriola, L. 1990. Immunocytochemical distribution of S-100 protein in patients with Down's syndrome. Acta Neuropathol. (Berl.) 80:475-478.
Griffin, W. S. T., Stanley, L. C., Ling, C., White, L., MacLeod, V., Perrot, L. J., White, C. L., and Araoz, C. 1989. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl. Acad. Sci. USA 86:7611-7615.
Goodison, K. L., Parhad, I. M., White, C. L. III, Sima, A. A., and Clark, A. W. 1993. Neuronal and glial gene expression in neocortex of Down's syndrome and Alzheimer's disease. J. Neuropathol. Exp. Neurol. 52:192-198.
Lefrancois, T., Fages, C., Peschanski, M., and Tardy M. 1997. Neuritic outgrowth associated with astroglial phenotypic changes induced by antisense glial fibrillary acidic protein (GFAP) mRNA in injured neuron-astrocyte cocultures. J. Neurosci. 17:4121-4128.
Chen, W. J. and Liem, R. K. 1994: Reexpression of glial fibrillary acidic protein rescues the ability of astrocytoma cells to form processes in response to neurons. J. Cell Biol. 127: 813-823.
Weinstein, D. E., Shelanski, M. L., and Liem, R. K. 1991. Suppression by antisense mRNA demonstrates a requirement for the glial fibrillary acidic protein in the formation of stable astrocytic processes in response to neurons. J. Cell Biol. 112:1205-1213.
Yu, A. C., Lee, Y. L., Eng, L. F. 1991. Inhibition of GFAP synthesis by antisense RNA in astrocytes. J. Neurosci. Res. 30(1):72-79.
Yu, A. C., Lee, Y. L., and Eng, L. F. 1993. Astrogliosis in culture: I. The model and the effect of antisense oligonucleotides on glial fibrillary acidic protein synthesis. J. Neurosci. Res. 34:295-303.
Ghirnikar, R. S., Yu, A. C., and Eng, L. F. 1994. Astrogliosis in culture: III. Effect of recombinant retrovirus expressing antisenseglial fibrillary acidic protein RNA. J. Neurosci. Res. 38:376-385.
Rutka, J. T., Hubbard, S. L., Fukuyama, K., Matsuzawa, K., Dirks, P. B., and Becker, L. E. 1994. Effects of antisense glial fibrillary acidic protein complementary DNA on the growth, invasion and adhesion of human astrocytoma cells. Cancer Res. 54:3267-3272.
Rutka, J. T., Ackerley, C., Hubbard, S. L., Tilup, A., Dirks, P. B., Jung, S., Ivanchuk, S., Kurimoto, M., Tsugu, A., and Becker, L. E. 1998. Characterization of glial filament-cytoskeletal interactions in human astrocytomas: an immuno-ultrastructural analysis. European J. Cell Biol. 76:279-287.
Rutka, J. T., Ivanchuk, S., Mondal, S., Taylor, M., Sakai, K., Dirks, P., Jun, P., Jung, S., Becker, L. E., and Ackerley, C. 1999. Co-expression of nestin and vimentin intermediate filaments in invasive human astrocytoma cells. International J. of Developmental Neurosci. 17:503-515.
Beguin, P., Shooter, E. M., and Eng, L. F. 1980. Cell-free synthesis of glial fibrillary acidic protein. Neurochem. Res. 5:513-521.
Deck, J. H. N., Eng, L. F., and Bigbee, J. 1976. A preliminary study of glioma morphology using the peroxidase-antiperoxidase method for the GFA protein. J. Neuropathol. Exp. Neurol. 35:362.
Deck, J. H. N., Eng, L. F., Bigbee, J., and Woodcock, S. M. 1978. The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Acta Neuropathol. (Berl.) 42:183-190.
Duffy, P. E., Graf, L., and Rapport, M. M. 1977. Identification of glial fibrillary acidic protein by the immunoperoxidase method in human brain tumors. J. Neuropathol. Exp. Neurol. 36:645-652.
Eng, L. F. and Rubinstein, L. J. 1978. Contribution of immunohistochemistry to diagnostic problems of human cerebral tumors. J. Histochem. Cytochem. 26:513-522.
Amaducci, L., Forno, K. I., and Eng, L. F. 1981. Glial fibrillary acidic protein in cryogenic lesions of the rat brain. Neurosci. Letts. 21:27-32.
Smith, M. E., Somera, F. P., and Eng, L. F. 1983. Immunocytochemical staining for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis. Brain Res. 264:241-253.
Cutler, R. W. P., Lorenzo, A. V., and Barlow, C. F. 1967. Brain vascular permeability to I125 gamma globulin and leukocytes in allergic encephalomyelitis. J. Neuropathol. Exp. Neurol. 26:558-571.
Juhler, M., Barry, D. I., Offner, H., Konat, G., Klinken, L., and Paulson, O. B. 1984. Blood-brain and blood-spinal cord barrier permeability during the course of experimental allergic encephalomyelitis in the rat. Brain Res. 302:347-355.
Kimelberg, H. K., Bourke, R. S., Stieg, P. E., Barron, K. D., Hirata, H., Pelton, E. W., and Nelson, L. R. 1982. Swelling of astroglia after injury to the central nervous system: Mechanisms and consequences. In R. G. Grossman and P. L. Gildenberg (Eds.), Head Injury: Basic and Clinical Aspects, pp. 31-44. Raven Press, New York.
Lee, J. C. 1982. Anatomy of the blood-brain barrier under normal and pathological conditions. In W. Haymaker and R. D. Adams (Eds.), Histology and Histopathology of the Nervous System, pp. 798-890. Charles Thomas
Miquel, J., Foncin, J.-F., Gruner, J. E., and Lee, J. C. 1982. Cerebral edema. In W. Haymaker and R. D. Adams (Eds.), Histology and Histopathology of the Nervous System, Charles Thomas, pp. 871-919.
Eng, L. F., D'Amelio, F. E., and Smith, M. E. 1989. Dissociation of GFAP intermediate filaments in EAE: Observations in the lumbar spinal cord. Glia 2:308-317.
Lewis, S. A. and Cowan, N. J. 1985. Temporal expression of mouse glial fibrillary acidic protein mRNA studied by a rapid in situ hybridization procedure. J. Neurochem. 45:913-919.
Hagiwara, N., Imada, S., and Sueoka, N. 1993. Cell type specific segregation of transcriptional expression of glial genes in the rat peripheral neurotumor RT4 cell lines. J. Neurosci. Res. 36:646-656.
Condorelli, D. F., Nicoletti, V. G., Barresi, V., Conticello, S. G., Caruso, A., Tendi, E. A., and Giuffrida Stella, A. M. 1999. Structural features of the rat GFAP gene and identification of a novel alternative transcript. J. Neurosci. Res. 56: 219-228.
Mucke, L. and Rockenstein, E. M. 1993. Prolonged delivery of transgene products to specific brain regions by migratory astrocyte grafts. Transgenics 1:3-9.
Holland, E. C. and Varmus, H. E. 1998. Basic fibroblast growth factor induces cell migration and. Proc. Natl. Acad. Sci. USA 95:1218-1223.
Carpenter, M. K., Winkler, C., Fricker, R., Emerich, D. F., Wong, S. C., Greco, C., Chen, E. Y., Chu, Y., Kordower, J. H., Messing, A., Bjorklund, A., and Hammang, J. P. 1997. Generation and transplantation of EGF responsive neural stem cells. Exp. Neurol. 148:187-204.
Kordower, J. H., Chen, E. Y., Winkler, C., Fricker, R., Charles, V., Messing, A., Mufson, E. J., Wong, S. C., Rosenstein, J. M., Bjorklund, A., Emerich, D. F., Hammang, J., and Carpenter, M. K. 1997. Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF. J. Comp. Neurol. 387:96-113.
McKie, E. A., Graham, D. I., and Brown, S. M. 1998. Selective astrocytic transgene expression in vitro and in vivo from. Gene Therapy 5:440-450.
Gomes, F. C., Garcia-Abreu, J., Galou, M., Paulin, D., and Moura Neto, V. 1999. Neurons induce GFAP gene promoter of cultured astrocytes from transgenic mice. Glia 26:97-108.
Quintana, J. G., Lopez-Colberg, I., and Cunningham, L. A. 1998. Use of GFAP-lacZ transgenic mice to determine astrocyte fate in grafts of embryonic ventral midbrain. Brain Res. Dev. Brain Res. 105:147-151.
Sun, Y., Wu, S., Bu, G., Onifade, M. K., Patel, S. N., LaDu, M. J., Fagan, A. M., and Holtzman, D. M. 1998. Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic. J. Neurosci. 18:3261-72.
Smith, J. D., Sikes, J., and Levin, A. J. 1998. Human apolipoprotein E allele-specific brain expressing transgenic mice. Neurobiology of Aging 19:407-413.
Delaney, C. L., Brenner, M., and Messing, A. 1996. Conditional ablation of cerebellar astrocytes in postnatal transgenic mice. J. Neurosci. 16:6908-18.
Bush, T. G., Puvanachandra, N., Horner, C. H., Polito, A., Ostenfeld, T., Svendsen, C. N., Mucke, L., Johnson, M. H., and Sofroniew, M. V. 1999. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scarforming, reactive astrocytes in adult transgenic mice. Neuron 23:297-308.
Galbreath, E., Kim, S. J., Park, K., Brenner, M., and Messing, A. 1995. Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus. J. Neuropathol. Exp. Neurol. 54:339-349.
Segovia, J., Vergara, P., and Brenner, M. (1998). Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental Parkinsonism. Gene Therapy 5:1650-1655.
Trejo, F., Vergara, P., Brenner, M., and Segovia, J. 1999. Gene therapy in a rodent model of Parkinson's disease using differentiated C6 cells expressing a GFAP-tyrosine hydroxylase transgene. Life Sciences 65:483-491.
Cortez, N., Trejo, F., Vergara, P., and Segovia, J. 2000. Primary astrocytes retrovirally transduced with a tyrosine hydroxylase transgene driven by a glial-specific promoter elicit behavioral recovery in experimental Parkinsonism. J. Neurosci. Res. 59:39-46.
Yao, C. P., Allen, J. W., Conklin, D. R., and Aschner, M. 1999. Transfection and overexpression of metallothionein-I in neonatal rat primary astrocyte cultures and in astrocytoma cells increases their resistance to methylmercury-induced cytotoxicity. Brain Res. 818:414-420.
Carr, D. J., Veress, L. A., Noisakran, S., and Campbell, I. L. 1998. Astrocyte targeted expression of IFN-alpha 1 protects mice from acute ocular herpes simplex virus type 1 infection. J. Immunol. 161:4859-4865.
Carrasco, J., Hernandez, J., Gonzalez, B., Campbell, I. L., and Hidalgo, J. 1998. Localization of metallothionein-I and-III expression in the CNS of transgenic mice with astrocyte-targeted expression of interleukin 6. Exp. Neurol. 153:184-194.
Lundkvist, J., Sundgren-Andersson, A. K., Tingsborg, S., Ostlund, P., Engfors, C., Alheim, K., Bartfai, T., Iverfeldt, K., and Schultzberg, M. 1999. Acute-phase responses in transgenic mice with CNS overexpression of IL-1 receptor antagonist. Am. J. Physiol. 276:R644-651.
Campbell, I. L. 1998. Transgenic mice and cytokine actions in the brain: bridging the gap between structural and functional neuropathology. Brain Res. Brain Res. Reviews 26:327-336.
Ramer, M. S., Kawaja, M. D., Henderson, J. T., Roder, J. C., and Bisby, M. A. 1998. Glial overexpression of NGF enhances neuropathic pain and adrenergic sprouting into DRG following chronic sciatic constriction in mice. Neurosci. Lett. 251: 53-56.
Raeber, A. J., Race, R. E., Brandner, S., Priola, S. A., Sailer, A., Bessen, R. A., Mucke, L., Manson, J., Aguzzi, A., Oldstone, M. B. et al. 1997. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO J. 16:6057-6065.
Iwaki, T., Kume-Iwaki, A., Liem, R. K. H., and Goldman, J. E. 1993. alpha-beta crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers. Am. J. Pathol. 143:487-495.
Messing, A., Head, M. W., Galles, K., Galbreath, E. J., Goldman, J. E., and Brenner, M. 1998. Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am. J. Pathol. 152:391-398.
Brenner, M., Johnson, A. B., Boespflug-Tanguy, O., Rodriguez, D., Goldman, J. E., and Messing, A. 2000. Mutations in GFAP associated with infantile, juvenile, and adult form of Alexander's Disease. (Abstr.) J. Neurochem. 74(Suppl.): S4B.
Pekny, M., Leveen, P., Pekna, M., Eliasson, C., Berthold, C. H., Westermark, B., and Betsholtz, C. 1995. Mice lacking GFAP display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J. 14:1590-1598.
Gomi, H., Yokoyama, T., Fujimoto, K., Ikeda, T., Katoh, A., Itoh, T., and Itohara, S. 1995. Mice devoid of the Glial fibrillary acidic protein develop normally and are suseptible to scrapie prions. Neuron 14:29-41.
Liedtke, W., Edelmann, W., Bieri, P. L., Chiu, F. C., Cowan, N. J., Kucherlapati, R., and Raine, C. S. 1996. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 17:607-615.
McCall, M. A., Gregg, R. G., Behringer, R. R., Brenner, M., Delaney, C. L., Galbreath, E. J., Zhang, C. L., Pearce, R. A., Chiu, S. Y., and Messing, A. 1996. Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc. Natl. Acad. Sci. USA 93:6361-6366.
Pekny, M., Eliasson, C., Chien, C. L., Kindblom, L. G., Liem, R., Hamberger, A., and Betsholtz, C. 1998. GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density. Expt. Cell Res. 239:332-343.
Tatzelt, J., Maeda, N., Pekny, M., Yang, S. L., Betsholtz, C., Eliasson, C., Cayetano, J., Camerino, A. P., DeArmond, S. J., and Prusiner, S. B. 1996. Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein. Neurol. 47: 449-453
Pekny, M., Johansson, C. B., Eliasson, C., Stakeberg, J., Wallen, A., Perlmann, T., Lendahl, U., Betsholtz, C., Berthold, C. H., and Frisen, J. 1999. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145:503-514.
Galou, M., Colucci-Guyon, E., Ensergueix, D., Ridet, J. L., Gimenez y Ribotta, M., Privat, A., Babinet, C., and Dupouey, P. 1996. Disrupted glial fibrillary acidic protein network in astrocytes from vimentin knockout mice. J. Cell Biol. 133: 853-863.
Ding, M., Eliasson, C., Betsholtz, C., Hamberger, A., and Pekny, M. 1998. Altered taurine release following hypotonic stress in astrocytes from mice deficient for GFAP and vimentin. Brain Res. Molec. Brain Res. 62:77-81.
Shibuki, K., Gomi, H., Chen, L., Bao, S., Kim, J. J., Wakatsuki, H., Fujisaki, T., Fujimoto, K., Katoh, A., Ikeda, T., Chen, C., Thompson, R. F., and Itohara, S. 1996. Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice. Neuron 16:587-599.
Liedtke, W., Edelmann, W., Chiu, F. C., Kucherlapati, R., and Raine, C. S. 1998. 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. Am. J. Pathol. 152:251-259.
Nawashiro, H., Messing, A., Azzam, N., and Brenner, M. 1998. Mice lacking GFAP are hypersensitive to traumatic cerebrospinal injury. NeuroReport. 9:1691-1696.
Wang, X., Messing, A., and David, S. 1997. Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein. Expt. Neurol. 148:568-576.
Raine, C. S. 1985. Editorial, J. Neuroimmunol. 8:(Issue 4-6).
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Eng, L.F., Ghirnikar, R.S. & Lee, Y.L. Glial Fibrillary Acidic Protein: GFAP-Thirty-One Years (1969–2000). Neurochem Res 25, 1439–1451 (2000). https://doi.org/10.1023/A:1007677003387
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DOI: https://doi.org/10.1023/A:1007677003387