The retinal degeneration (rd) gene seriously impairs spatial cognitive performance in normal and Alzheimerʼs transgenic mice

To determine the effects of the recessive retinal degeneration (rd) gene on behavioral performance, three Alzheimerʼs transgenic lines (APPsw, P30lL, APPsw+P301L) and non-transgenic littermates were evaluated in a comprehensive behavioral battery between 5 and 8.5 months of age. For all four genotypes collectively, rd homozygosity resulted in profound impairment in spatial cognitive tasks requiring visual acuity (Morris maze, platform recognition, and radial arm water maze). Non-transgenic and P301L mutant tau mice contributed most to this rd effect since heterozygous and wild type mice performed well. By contrast, spatial cognitive performance of both APPsw-expressing lines was often impaired, irrespective of rd status. Sensorimotor performance was unaffected by rd homozygosity, while rd effects on anxiety were genotype-dependent (less anxiety in NT, APPsw; more anxiety in P301L, APPsw+P301L). Our results strongly encourage rd screening of genetically manipulated mouse lines produced from rd-carrying strain backgrounds to avoid serious potential confounds in the interpretation of spatially based cognitive performance.