Assessment of Memory in the DP(16)1YEY/+ Mouse Model of Down Syndrome

Abstract

Down syndrome (DS) is a common genetic condition caused by the presence of three copies of chromosome 21 (trisomy 21). DS greatly increases the risk of Alzheimer’s disease (AD), and a large percentage of people with DS develop AD neuropathology by the age of 40. To investigate the genetic contribution of trisomy 21 to DS phenotypes, including those related to AD pathology, a range of DS mouse models have been generated consisting of mice that are trisomic for chromosome segments syntenic to human chromosome 21 (Hsa21). The objective of the current study was to determine whether the working and spatial memory impairments seen in AD and AD mouse models are also present in the Dp(16)1Yey/+ mouse model of DS. In this model, the entire Hsa21 orthologous region on mouse chromosome 16 (Mmu16) (∼119 genes), has been duplicated and added onto the distal portion of one of the endogenous Mmu16 chromosomes. Recognition memory was assessed using the novel object recognition (NOR) task, spatial working memory by spontaneous alternations in the Y-Maze task, and spatial reference memory using the Morris Water Maze (MWM) task. The light/dark box was used to assess anxiety-like behavior. Behavioural testing was performed at 4, 6, and 9 months of age in Dp(16)1Yey/+ mice and age-matched wildtype littermates. The results of the light/dark box test indicated that Dp(16)1Yey/+ mice exhibited increased anxiety-like behaviour, an important non-cognitive behavioral deficit associated with AD. In the NOR and Y-maze tasks, Dp(16)1Yey/+ mice demonstrated no difference in performance compared to wildtype mice. Similarly, in the MWM task, there were no statistically significant differences in performance between genotypes in both hidden and cued platform trials and in the probe trial. Although investigators reported results to the contrary, based on the results of the present study we would conclude that the Dp(16)1Yey/+ DS mouse model thus does not represent a useful comparator for assessing the memory deficits seen in AD and AD mouse models.