Normal and pathological expression of GFAP promoter elements in transgenic mice

Abstract

The expression of the glial fibrillary acidic protein (GFAP), a component of astroglial intermediate filaments, is regulated under developmental and pathological conditions. In order to characterize DNA sequences involved in such regulations, we produced transgenic mice bearing 2 kb of the 5' flanking region of the murine GFAP gene linked to the Escherichia coli beta-galactosidase (beta-gal) reporter gene. Seven transgenic lines were obtained. We observed that the regulatory elements present in the transgene GFAP-nls-LacZ direct an expression in the neural and non-neural tissue and target in vivo an unexpected subpopulation of astrocyte. In the developing brain, beta-gal activity and GFAP appeared simultaneously and in the same region, on embryonic day 18 (E18), suggesting that the 2 kb of the promoter contains the regulatory sequences responsible for the perinatal vimentin/GFAP switch. In addition, we demonstrated that the 2 kb sequence of the GFAP promoter used in the transgene possess elements which are activated after a surgical injury, thus permitting to study some aspects of reactive gliosis in these transgenic mice. These transgenic lines provide a useful tool by enabling further studies of astroglial and, probably, neuronal physiologies.

Neuropathologies in Transgenic Mice Expressing Human Immunodeficiency Virus Type 1 Tat Protein under the Regulation of the Astrocyte-Specific Glial Fibrillary Acidic Protein Promoter and Doxycycline

“…The amplification products of genomic DNA in these nonbrain tissues or organs was confirmed to be nonspecific by Southern blot analysis using a TRE-Tat transgene-specific DNA probe (data not shown). Moreover, consistent with the astroglial GFAP expression pattern, 58,59 in situ hybridization detected higher levels of Tat mRNA in the cerebellum, cerebellar cortex, hippocampus, brain stem, tectum, and white matter tracts in the brains of GT-tg bigenic mice treated with Dox, much fewer Tat mRNA transcripts in the brains of GT-tg bigenic mice treated without Dox, and no Tat mRNA transcripts in the brains of wild-type mice (data not shown).…”

Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental Parkinsonism

“…[32][33][34][35] Use of the GFAP promoter permits these cells to be specifically targeted in vivo. Another attribute of the GFAP promoter is that its activity increases in response to extracellular signals that induce reactive gliosis, 18,36,37 or increase intracellular cAMP. 38,39 It is thus likely that transcription from a gfa2-regulated transgene will be stimulated in response to gliosis, generating a feedback mechanism in which an increase in the damage induced by a disease will up-regulate the transcription of the ameliorating transgene.…”

Glial and Perivascular Structures in the Subfornical Organ

“…Otherwise, where vimentin occurs in the astrocytes of the mature brain (corpus callosum, Bergmann-glia, reactive glia; see Schnitzer et al 1981;Janeczko 1993), it is co-localized with GFAP. Different intermediate filament compositions indicate different features and functions of the end-feet (Galou et al 1994;Menet et al 2001). Pixley and de Vellis (1984) suggested, for example, that vimentin-containing glial processes are especially capable of transport from fluid compartments.…”