A transcriptional enhancer of the glutamine synthetase gene that is selective for retinal Muller glial cells

This article demonstrates that the chicken glutamine synthetase (GS) promoter contains cis-acting elements that direct transcription to retinal Muller glial cells. The transient assay system developed to identify these elements involved electroporation of intact retinal tissue with GS-beta-galactosidase fusion genes followed by preparation of primary cultures and histochemical assay of cells expressing beta-galactosidase. Plasmids containing beta-galactosidase under transcriptional control by two different viral promoters are expressed primarily in neuronal cells after transfection of intact embryonic d 12 retina. In sharp contrast, expression is primarily in Muller glia after transfection with a GS-beta-galactosidase fusion gene. Although GS is glucocorticoid inducible, steroid hormone is not required to achieve Muller cell-selective expression of the GS-beta-galactosidase fusion gene. Deletion studies indicate that multiple cis-acting elements located between nucleotides -436 and -61 relative to the GS transcription start site contribute to produce Muller cell selectivity. Moreover, these upstream elements enhance expression of a heterologous promoter in Muller cells but not neurons. These results indicate that an enhancer located between 61 and 436 nucleotides upstream of the transcription start site contributes to Muller cell-selective expression of the GS gene in the retina.