Mice expressing the Swedish APP mutation on a 129 genetic background demonstrate consistent behavioral deficits and pathological markers of Alzheimer's disease.

ABSTRACT

Mutant Tg2576 mice which possess the human "Swedish" APP mutation have been shown to demonstrate both Abeta plaque pathology and memory deficits in behavioral tasks. These mice are routinely maintained on a mixed C57BL/6xSJL genetic background which exhibits a high frequency of retinal degeneration allele and high variability in many behavioral assays. The same APP mutation is also available maintained on a 129 genetic background, providing more genetic homogeneity, but little data are published regarding the effects of the mutation on this background. We investigated whether transgenic mice expressing the Swedish mutation on the 129 background show similar behavioral deficits and Abeta pathology as those on the mixed background. Mice on the 129 background were tested at 6-7, 11-12, or 18-19 months of age in locomotor activity, Y-maze spontaneous alternation, and contextual fear conditioning. Differences were detected between WT and Tg mice in locomotor activity at 6-7 and 18-19 months, Y-maze at 6-7 and 11-12 months, and fear conditioning at 6-7, 11-12, and 18-19 months. In contrast, Tg mice on the mixed B6/SJL background tested at 6-7 months only demonstrated significant impairment in the contextual fear conditioning assay and in the Y-maze in one of 2 cohorts tested. Despite the behavioral differences observed, similar Abeta pathology was observed between Tg mice on the two genetic backgrounds. These results indicate that mice on the 129 genetic background may generate more consistent and robust behavioral differences, providing a useful model for testing therapeutic agents for Alzheimer's disease.