Spatial learning in transgenic mice expressing human presenilin 1 (PS1) transgenes.
Dominant mutations in the Presenilin 1 gene are linked to an aggressive, early-onset form of familial Alzheimer's Disease (FAD). Spatial memory of transgenic (Tg) mice expressing either mutant (lines Tg(M146L)1, Tg(M146L)76, Tg(L286V)198) or wild type (line Tg(PS1wt)195) human PS1 transgenes was investigated in the Morris water maze (WM) test at 6 and 9 months of age. The results showed that the mutated Tg mice had increased swim speed when compared to non-Tg littermates or Tg PS1 wild type mice. The swim speed difference did not, however, significantly affect the spatial learning in the WM test and all groups showed comparable search paths during training and similar spatial bias during probe trials. When re-tested at 9 months, all mice showed significantly improved learning acquisition of spatial information. The lack of progressive spatial learning impairment in mice expressing the mutated human PS1 transgene in the WM does not preclude impairments in other cognitive tasks but suggests that full phenotypic expression of mutant PS1 alleles may require co-expression of human versions of other AD-associated genes.
Centre for Research in Neurodegenerative Disease, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Cr. W., M5S 3H2, Toronto, Ontario, Canada. janus@psych.utoronto.ca
C
C
Janus
S
S
D'Amelio
O
O
Amitay
M A
MA
Chishti
R
R
Strome
P
P
Fraser
G A
GA
Carlson
J C
JC
Roder
P
P
St George-Hyslop
D
D
Westaway
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D003071:Cognition; D004193:Discrimination Learning / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D018782:Maze Learning / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1; D013028:Space Perception / Q000502:physiology*; D013550:Swimming; D019076:Transgenes / Q000235:genetics
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1