Background - Mouse Mutations Causing Eye and Vision Defects
Genetics of vision and ocular disorders, contribution of mouse models - Except for trauma and infectious diseases, the majority of reported human eye diseases are genetic in nature [184, 185]. Many do not have corresponding animal models. Animal models are important for identification of the molecular basis of disease, for elucidation of pathways in which particular genes function and for testing therapeutic intervention. They are also especially important in eye research because of the inaccessibility of human eye tissue to study the pathological progression of disease and, ultimately, to understand normal eye biology.
The need for animal models is clear and their central role in understanding human disease permeates the literature. For example, genes that lead to retinal degeneration - myosin VIIa, peripherin, and rod cGMP phosphodiesterase, ß-subunit - were first identified as mouse mutations - shaker1, Rds, and rd1, respectively [162, 186-188]. Once each was identified, the similarity of phenotypes and knowledge of homologous chromosomal location between mouse and humans led to the identification of mutations in the orthologous human genes [159, 189]; [190]. Additionally, the mouse genome can be genetically altered when spontaneous mutations do not yet exist. For example, transgenics for a mutant allele of rhodopsin have been used to examine the role of apoptosis on retinal degeneration [191]. Together, spontaneous, transgenic and targeted mutant mice have provided valuable insight into the function of genes in normal vision. Mice with genetic diseases are also a renewable, reproducible resource. Tissue is available throughout development and during disease progression for pharmacological screening of drugs and for testing various therapeutic regimens such as gene therapy. Finally, in the mouse but not in human, genetic factors that interact with disease genes to vary their expression can be isolated and eventually identified [175, 176]. Understanding the "natural" gene interactions that can delay or suppress retinal degeneration or neovascularization, for example, may provide a blueprint for new therapies.
