Evaluation of the rhodopsin knockout mouse as a model of pure cone function

PURPOSE. To determine a time window in the rhodopsin knockout (Rho(-/-)) mo use during which retinal function is already sufficiently developed but con e degeneration is not yet substantial, thus representing an all-cone retina . METHODS. Electroretinograms (ERGs) were obtained from 14 homozygous Rho(-/- ) mice and eight C57Bl/6 control mice. The same individuals were tested eve ry 7 days, beginning as early as postnatal day (P)14. The ERG protocols inc luded flash and flicker stimuli, both under photopic and scotopic condition s. Retinal and choroidal morphology was observed in animals of comparable a ge. RESULTS. Functionally, the developmental phase lasted until postnatal week (PW)3 in both the Rho(-/-) mice and the control animals. During PW4 to 6, t he Rho(-/-) mice showed a plateau in ERG parameters with normal or even sup ernormal cone responses and complete absence of rod contributions. At PW7, there was a marked onset of degeneration, which progressed so that no ERG s ignals were left at PW13, when the control eyes still had normal ERG respon ses. Microscopically, cone degeneration paralleled the functional changes, beginning at approximately PW6 and almost complete at PW13, whereas retinal pigment epithelium (RPE) and choroid did not show am abnormalities. CONCLUSIONS. From PW4 to 6, Rho(-/-) mice appear to have normal cone and no rod function. Despite the missing rod outer segment (OS), the structure of retina, RPE, and choroid remained unchanged. Therefore, the Rho(-/-) mice can serve during this age period as a model for pure cone function. Such a model is particularly useful to evaluate rod-cone interaction and to dissec t rod- from cone-mediated signaling pathways in vivo.