Behavioral analyses of visually impaired Crx knockout mice revealed sensory compensation in exploratory activities on elevated platforms

Visual perception is important for acquiring spatial information in many animals, and loss of vision often causes devastating effects on their survival. However, it may be compensated to some extent by utilizing other intact sensory modalities. The cone-rod homeobox (Crx) gene plays a key role in development of photoreceptor cells, but behavioral consequences of the gene deletion have not been well characterized. In this study, we analyzed homozygous knockout (Crx^-/-) mice by comparing with heterozygous knockout (Crx^+/-) mice as controls. We first checked their vision with three different behavioral paradigms of the glass table visual recognition test, the light-dark transition test, and the Barnes maze test with a visual cue, all of which indicated that Crx^-/- mice were blind while Crx^+/- mice were sighted. In the fear conditioning test, Crx^-/- mice were able to acquire both contextual and cued memory using non-visual information. Crx^-/- mice showed normal thigmotaxis, but the exploratory activities were significantly increased. In the elevated plus maze test, it was unexpected that Crx^-/- mice rarely fell down from the narrow platform. There was no reduction in their moving speeds and the moving distance was rather increased in Crx^-/- mice. Such behaviors were not affected by trimming their whiskers. However, attachment of earplugs significantly reduced their exploratory activities. In summary, these data suggest that Crx^-/- mice were behaviorally blind but were able to learn and recognize external environment utilizing non-visual information, as exemplified by sensory compensation in exploratory activities on elevated platforms.