Altered expression of KIF17, a kinesin motor protein associated with NR2B trafficking, may mediate learning deficits in a Down syndrome mouse model.

Abstract

Down syndrome (DS), a major cause of mental retardation, affects 1 of 800 newborns. Mouse models for Down syndrome have been studied and found to have developmental and learning deficits, including the Ts65Dn (DS) mouse model. N-methyl-D-aspartate receptor NR2B subunit enhances synaptic plasticity. The up-regulation of KIF17, a motor protein that transports NR2B to the synaptic region parallels up-regulation of synaptic NR2B. Down regulation of KIF17 reflects up-regulation of less plastic NR2A subunit. We evaluated NR2B, NR2A, and KIF17 in Ts65Dn and control mice. Ts65Dn (4) and control (4) adult brains were collected; NR2A, NR2B, and KIF17 were measured by Western blot and quantified using National Institutes of Health Image software. Comparisons were made using analysis of variance, < .05 was considered significant. There was a significant decrease in KIF17 (P = .04) level in Ts65Dn mice as compared with the control animals, but there were no significant differences in the levels of NR2A (P = .79) and NR2B (P = .96). The significant decrease of KIF17 inTs65Dn animals may in part mediate cognitive defects in DS.