Three (Hundred) Blind Mice

Who would have guessed the key to understanding the human genome could fit into the palm of your hand? That key, of course, is the humble mouse – and it has just helped a team at the University of California, Davis, identify 347 new genes linked to visual function. The results are the latest to come from the International Mouse Phenotyping Consortium (IMPC), a global cooperative dedicated to identifying the function of every gene in the mammalian genome. So far, the IMPC has characterized more than 4,364 genes across 11 organ systems – a figure that is growing day by day.

Mice are often the heroes of genetic research, due to the similarity of their genome to our own – humans and mice share around 20,000 genes. “We identified dozens of ocular conditions that strongly resemble blinding eye diseases in people,” says Ala Moshiri, an assistant professor in ophthalmology and vision science at UC Davis, who helped run the study. “These include numerous mouse models of retinal degeneration diseases, like retinitis pigmentosa, as well as some unusual ocular conditions, including those that also affect other organ systems, such as the skin, kidneys, or musculoskeletal system.” Only 86 of the recently discovered genes were already known to be associated with vision, while three-quarters – 261 – were not previously implicated in eye health in any species (1).

Kent Lloyd, director of the UC Davis Mouse Biology Program and principal investigator of the Knockout Mouse Production and Phenotyping (KOMP2) project, explains how they did it: “Male and female knockout mice were created for each gene and analyzed using the standardized protocols shared by all IMPC member laboratories. Ophthalmological studies took place at 15 to 16 weeks of age, with ocular and adnexal structures examined by highly-trained and experienced technical support staff, including both human and animal ophthalmologists.”

The next step in the project – validating the genes in humans – is already underway, and the researchers hope that the process could eventually help provide answers to the families of the 25 to 50 percent of patients with presumed inherited blindness whose mutations cannot be identified after genome sequencing. “When each mouse gene is validated in a human family, the knockout mouse model for that exact condition will be immediately available to researchers,” says Moshiri, “so the mice are not only leading us to diagnosing new disease genes, they are also serving as an ideal testing ground for new therapies in this era of precision medicine.”