THE MGLUR6 5'-UPSTREAM TRANSGENE SEQUENCE DIRECTS A CELL-SPECIFIC ANDDEVELOPMENTALLY-REGULATED EXPRESSION IN RETINAL ROD AND ON-TYPE CONE BIPOLAR CELLS

We generated transgenic mice, using 9.5 kilobase pairs of the 5' upstr eam sequence from the mouse metabotropic glutamate receptor subtype 6 (mGluR6) gene fused to the beta-galactosidase (lacZ) reporter gene, an d investigated the promoter function of the cell-specific and developm entally regulated expression of mGluR6. Most of the independent transg enic lines commonly showed the lacZ expression in the defined cell lay ers of the retina, and four transgenic lines were characterized in det ail for cell-specific lacZ expression patterns by X-gal staining and l acZ immunostaining. The lacZ-expressing retinal cells were classified into two cell types. One cell type was identified as rod bipolar cells on the basis of colocalization of protein kinase C (PKC) immunoreacti vity and morphological criteria. The other cell type was PKC-immunoneg ative and resided at the cell layers corresponding precisely to ON-typ e cone bipolar cells. The latter bipolar cells were found to exist as a large cell population comparable to rod bipolar cells. This observat ion was confirmed by coimmunostaining of dissociated retinal cells wit h the lacZ and PKC antibodies. The ontogeny analysis indicated that th e lacZ expression completely agrees with a temporal expression pattern of mGluR6 during retinal development. This study demonstrates that th e mGluR6 5' upstream genomic sequence is capable of directing a cell-s pecific and developmentally regulated expression of mGluR6 in ON-type bipolar cells and supports the view that mGluR6 is responsible for ON responses in both the rod and cone systems.