Motor dysfunction in a mouse model for Down syndrome.
Motor deficits are among the most frequently occurring features of Down syndrome (DS). Individuals with DS exhibit disturbances in the dynamics of movement production and postural control that are thought to have a significant impact in delaying their acquisition of motor skills. The origin of these deficits has been hypothesized to be cerebellar. The Ts65Dn mouse is the most robust and genetically sound animal model for DS currently available. Ts65Dn mice show many DS-like features, including significant learning deficits in different behavioral tasks and neurodegeneration of cholinergic neurons. In the present study, we investigate the motor function of these animals. We have analyzed hind paw print patterns during walking, running speeds, rotarod performance, grip force production, swim paths, and swimming speeds. Our results indicate that Ts65Dn mice present mild to severe dysfunction according to all of the above assessments. The most evident impairments presented by these mice were related to equilibrium and motor coordination, which agrees with reported clinical observations made on individuals with DS. Because none of these findings were readily apparent by simple inspection of these animals, these findings reiterate the need for a careful evaluation of any mutant mouse strain for which there is reason to suspect motor deficits. The identification of motor dysfunction in Ts65Dn mice may have important consequences for the interpretation of some previous assessments of learning and memory of these animals that assumed intact motor function, and further strengthens the use of this aneuploid mouse strain as a model for DS.
Costa
A C
AC
The Jackson Laboratory, Bar Harbor, ME 04609 USA. acc@jax.org
Walsh
K
K
Davisson
M T
MT
D000818:Animals; D002531:Cerebellum / Q000503:physiopathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D018737:Hand Strength / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009048:Motor Skills / Q000502:physiology*; D009949:Orientation / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D011187:Posture / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology