Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities.
BACKGROUND
PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity.


RESULTS
We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls.


CONCLUSIONS
We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.
Ramos
Joe W
JW
Cancer Research Center of Hawaii, Department of Natural Products and Cancer Biology, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI 96813, USA. jramos@crch.hawaii.edu
Townsend
David A
DA
Piarulli
Dawn
D
Kolata
Stefan
S
Light
Kenneth
K
Hale
Gregory
G
Matzel
Louis D
LD
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001245:Association Learning / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D005239:Fear; D018737:Hand Strength / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009812:Odorants; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics*; D013037:Spatial Behavior / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C490444:Pea15 protein, mouse; D010750:Phosphoproteins