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


METHODS
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.


RESULTS
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).


CONCLUSIONS
The significant decrease of KIF17 inTs65Dn animals may in part mediate cognitive defects in DS.
Roberson
Robin
R
Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20895, USA. robersor@mail.nih.gov
Toso
Laura
L
Abebe
Daniel
D
Spong
Catherine Y
CY
D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016547:Kinesins / Q000096:biosynthesis* / Q000235:genetics*; D007859:Learning Disabilities / Q000235:genetics*; D008297:Male; D051379:Mice; D020409:Molecular Motor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D021381:Protein Transport; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
C409642:KIF17 protein, mouse; D020409:Molecular Motor Proteins; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016547:Kinesins