THE HUMAN BLUE OPSIN PROMOTER DIRECTS TRANSGENE EXPRESSION IN SHORT-WAVE CONES AND BIPOLAR CELLS IN THE MOUSE RETINA

Transgenic mouse lines were generated using either 3.8 or 1.1 kb of 5' upstream flanking sequence from the human blue opsin gene fused to th e lacZ or human growth hormone reporter gene. Mice were analyzed for a ppropriate cell-specific and developmental expression patterns. In 13 independently derived lines of animals, transgene expression was limit ed to photoreceptor and inner nuclear layer cells. Photoreceptors were identified as cone cells based on morphological criteria and colocali zation of transgene expression with the cone-associated marker, peanut agglutinin lectin. More specifically, transgene-positive photorecepto rs were identified as short-wave cone cells (S-cones) by using the sho rt-wave color opsin-specific antibody, OS-2. Reporter-gene-positive ce lls of the inner nuclear layer were identified as bipolar cells based on morphological criteria. Transgenes and the endogenous mouse short-w ave opsin gene were transcriptionally coactivated at embryonic day 13. These results show that 3.8 or 1.1 kb of human blue opsin upstream fl anking sequences are capable of directing expression in short-wave con e cells in a spatially and temporally appropriate fashion and that the human blue opsin gene is the homologue of the short-wave-sensitive pi gment, S-opsin, in the short-wave cones of the mouse retina. Expressio n in the bipolar cells may reflect regulatory mechanisms that are comm on to these cells and to the cone photoreceptors.