Recently developed experimental methods in which functional foreign genes are introduced into the germ line of mammals provide a powerful new tool for dissecting complex biological processes. These techniques have great potential for providing a new approach for the study of basic visual mechanisms. The research proposed here will introduce human cone pigment genes into mongolian gerbils (Meriones unguiculatus) with the aim of producing gerbils that express human pigments in their cone outer segments. The gerbil is uniquely suited for this project. It has a robust photopic system but only a single type of cone photopigment. The spectral peak of the gerbil cone pigment (494 nm) is well separated from that of any of the human cone photopigments. Thus, the presence of introduced human cone pigments will be easily detected in the gerbil even at low levels of expression. The proposed research will employ methods involving the production of transgenic gerbils and the subsequent assessment of the consequences of the introduced genes on visual function as follows: Cone pigment genes isolated from a human genomic library will be microinjected into gerbil embryos. The expression of the introduced genes in the resulting gerbils will be assayed by a retinal gross potential, the electroretinogram. Gerbils that express the human photopigment transgene will be further examined in behavioral experiments and direct photopigment measurements will be made using microspectrophotometry of cone outer segments. If human cone pigment genes can be expressed in gerbils, this work will provide the first step toward future experiments designed to elucidate the mechanisms involved in the developmental regulation of cone pigment gene expression with the particular aim of understanding errors in photopigment gene expression that underlie visual defects. This work will also provide a starting point for experiments designed to further illuminate the neural mechanisms of color vision.
| Jacobs, G H; Neitz, J (1989) Cone monochromacy and a reversed Purkinje shift in the gerbil. Experientia 45:317-9 |
