Structure and transcriptional regulation of the GFAP gene.
Transcriptional regulation of the GFAP gene is intimately connected with astrocyte function: its initial activation marks the differentiation of astrocytes, and its up-regulation accompanies the reactive response to CNS injury. Studies of GFAP transcription should thus provide insights into multiple regulatory pathways operating in these cells. In addition, they should identify DNA elements that could be used to direct synthesis of other proteins to astrocytes in transgenic animals, permitting creation of disease models, and the testing of cause and effect relationships. This review describes several GFAP cDNA and genomic clones that have been isolated, including homology comparisons of the encoded RNAs and proteins. Cell transfection studies by several laboratories are summarized that have identified a DNA segment immediately upstream of the RNA start site that is essential for transcriptional activity, but which have yielded conflicting results concerning the importance of other segments located both further upstream and downstream of the RNA start site. Two procedures are recounted that have led to the successful expression of GFAP-transgenes in astrocytes in mice. One of these incorporates the transgene into the first exon of a fragment spanning the entire GFAP gene, while the other links it to a 2 kb 5'-flanking segment. Results already produced by GFAP-transgenic studies include demonstration of a neurotoxic effect of the HIV-1 gp120 coat protein, and creation of a hydrocephalic mouse model.
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
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Brenner
D000818:Animals; D030801:Animals, Genetically Modified; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000633:toxicity; D015497:HIV-1; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000633:toxicity; D011401:Promoter Regions, Genetic; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D014158:Transcription, Genetic; D014162:Transfection
D005904:Glial Fibrillary Acidic Protein; D015699:HIV Envelope Protein gp120; D009498:Neurotoxins