Differential regulation of a glial fibrillary acidic protein-LacZ transgene in retinal astrocytes and Müller cells.
OBJECTIVE
Glial fibrillary acidic protein (GFAP) is normally expressed in astrocytes, but not in Müller cells, in the mouse retina. In response to retinal injury or photoreceptor degeneration, however, GFAP gene transcription is strongly activated in the Müller cell. To identify the genetic elements involved in GFAP gene induction, the authors have studied gene expression in transgenic mice in which beta-galactosidase (beta-gal) expression is under control of GFAP regulatory sequences.


METHODS
Histochemical methods were used to study gene expression. The transgene expression was followed by x-gal staining, whereas GFAP expression was monitored by immunostaining with GFAP antibody.


RESULTS
In GFAP-LacZ transgenic mice, beta-gal activity and GFAP immunostaining were found in retinal astrocytes. Transgene expression showed the same developmental pattern as that of endogenous GFAP in retinal astrocytes. In addition, beta-gal staining also was observed in lens epithelial cells. Neither GFAP nor beta-gal expression was seen in Müller cells in the adult or developing retina. When focal retinal lesions were introduced into the retina, strong GFAP immunostaining was observed in Müller cells throughout the retina. No beta-gal staining was seen in Müller cells in these retinas. In astrocytes, however, beta-gal and GFAP both were present.


CONCLUSIONS
The observations suggest that cis elements responsible for GFAP expression in retinal astrocytes are present in 5' flanking region of the GFAP gene, whereas the regulatory elements involved in GFAP induction in Müller cells are located elsewhere.
Verderber
L
L
Department of Ophthalmology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Johnson
W
W
Mucke
L
L
Sarthy
V
V
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D006651:Histocytochemistry; D007124:Immunoenzyme Techniques; D007763:Lac Operon; D007908:Lens, Crystalline / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; D001616:beta-Galactosidase