NORMAL AND PATHOLOGICAL EXPRESSION OF GFAP PROMOTER ELEMENTS IN TRANSGENIC MICE

The expression of the glial fibrillary acidic protein (GFAP), a compon ent of astroglial intermediate filaments, is regulated under developme ntal and pathological conditions. In order to characterize DNA sequenc es involved in such regulations, we produced transgenic mice bearing 2 kb of the 5' flanking region of the murine GFAP gene linked to the Es cherichia coli beta-galactosidase (beta-gal) reporter gene. Seven tran sgenic lines were obtained. We observed that the regulatory elements p resent in the transgene GFAP-nls-LacZ direct an expression in the neur al and non-neural tissue and target in vivo an unexpected subpopulatio n of astrocyte. In the developing brain, beta-gal activity and GFAP ap peared simultaneously and in the same region, on embryonic day 18 (E18 ), suggesting that the 2 kb of the promoter contains the regulatory se quences responsible for the perinatal vimentin/GFAP switch. In additio n, we demonstrated that the 2 kb sequence of the GFAP promoter used in the transgene possess elements which are activated after a surgical i njury, thus permitting to study some aspects of reactive gliosis in th ese transgenic mice. These transgenic lines provide a useful tool by e nabling further studies of astroglial and, probably, neuronal physiolo gies. (C) 1994 Wiley-Liss, Inc.