Behavioral assessment of the Ts65Dn mouse, a model for down syndrome: Altered behavior in the elevated plus maze and open field

Abstract

The Ts65Dn mouse carries a partial trisomy for mouse chromosome 16 in a region that has high homology to the Down syndrome (DS) region of human chromosome 21 and is, thus, a potential animal model of DS. The focus of the present study was to begin to characterize the behavioral phenotype of this mouse to assess its usefulness as a model of aspects of the DS phenotype. The behavior of Ts65Dn and littermate control mice was assessed in the elevated plus maze, lighted and dark open field, and a step-down passive avoidance task. The behavior of Ts65Dn mice in these tests differed considerably from the nontrisomic controls. In the elevated plus maze, Ts65Dn had more total arm visits than controls, showed a higher percentage of arm visits to the open arms than control mice, and showed no preference for the closed arms. Ts65Dn mice were more active in both open-field situations, regardless of light condition, and ventured into the center of the arena more than controls. Lighting in the open field had moderate effects on the activity of the Ts65Dn mice, but control mice were, as expected, much more active in the dark than the light. The trisomic mice learned and retained the step-down passive avoidance task in the same number of trials as the controls. Overall, these data indicate that Ts65Dn mice are more active than control mice in two testing situations. Most striking is the finding that the Ts65Dn mice were much less responsive to variations in environmental cues to which normal mice are quite sensitive. These data not only begin to characterize systematically the Ts65Dn phenotype, but also raise several interesting issues about the sources of the aberrant behaviors observed in these mice.

Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

“…There is precedence for this view, as the Ts65Dn mutant mouse also demonstrates greatly increased motor output with corresponding anxiolytic-like EPM results. Because of the hyperactivity, however, these changes have been interpreted not as anxiety, but as a lack of behavioral inhibition or reduced attention to environmental stimuli [7,33]. While recognizing that a simple explanation would involve primary disruption of the anxiety state, we suggest that Lsamp −/− mice exhibit heightened reactivity to stressful stimuli, revealed by hyper-activation and lack of appropriate behavioral inhibition.…”

The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice

“…Overexpression of HMGN1 leads to hyperactivity, reduced anxiety, and abnormal social interest, some of the behavioral phenotypes detected in mouse models for Down syndrome (49). Conversely, Hmgn1 Ϫ/Ϫ mice display hypoactivity and abnormal social behavior and overall demonstrate features that resemble behaviors seen in models of ASDs (42).…”

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

“…However, learning and memory are not impaired in all tasks. Cued learning in the swim task is preserved in the Ts65Dn mice (Escorihuela et al, 1995;Sago et al, 2000), as is memory needed to discriminate very dissimilar contexts (Hyde and Crnic, 2001) and memory for inhibitory avoidance training (Coussons-Read and Crnic, 1996).…”