On the genetics of retinal function and disease

Abstract

There are many recorded examples in which genetic background has been shown to radically influence retinal phenotypes in inbred mouse strains. For example, the manifestations of a targeted knockout of the p53 gene are much more severe in mice on a C57 background compared with those on a 129 background. Similarly, the retinal degeneration occurring in Rho-/- mice is less severe on a C57 than on a 129 congenic background. The retina is by no means unique in this respect. In the majority of diseases so far investigated in murine models, genetic background plays a major role in disease severity. In many cases, such variability is the likely result of the presence of the effects of so-called 'modifier genes' which exert variable effects on one background or another to modulate a given phenotype. Identification of such genes, particularly if relating to retinal function or structure is a potentially important endeavour, since an understanding of their function may bear direct relevance to our understanding of important retinal processes such as visual transduction, or the severity of disease symptoms induced by primary mutations.