title: Extracellular signal-regulated kinase 2 (ERK2) knockdown mice show deficits in long-term memory; ERK2 has a specific function in learning and memory.
abstract: The extracellular signal-regulated kinase (ERK) 1 and 2 are important signaling components implicated in learning and memory. These isoforms display a high degree of sequence homology and share a similar substrate profile. However, recent findings suggest that these isoforms may have distinct roles: whereas ERK1 seems to be not so important for associative learning, ERK2 might be critically involved in learning and memory. Thus, the individual role of ERK2 has received considerable attention, although it is yet to be understood. Here, we have generated a series of mice in which ERK2 expression decreased in an allele dose-dependent manner. Null ERK2 knock-out mice were embryonic lethal, and the heterozygous mice were anatomically impaired. To gain a better understanding of the influence of ERK2 on learning and memory, we also generated knockdown mice in which ERK2 expression was partially (20-40%) reduced. These mutant mice were viable and fertile with normal appearance. The mutant mice showed a deficit in long-term memory in classical fear conditioning, whereas short-term memory was normal. The mice also showed learning deficit in the water maze and the eight-arm radial maze. The ERK1 expression level of the knockdown mice was comparable with the wild-type control. Together, our results indicate a noncompensable role of ERK2-dependent signal transduction in learning and memory.
authors.affiliation: Department of Biochemistry, National Defense Medical College, Tokorozawa 359-8513, Japan. ys@ndmc.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Shogo
authors.initials: S
authors.lastname: Endo
authors.forename: Toshio
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Masataka
authors.initials: M
authors.lastname: Ito
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiramoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Imamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Kunio
authors.initials: K
authors.lastname: Takishima
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D049229:Dendritic Spines / Q000473:pathology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D005786:Gene Expression Regulation / Q000235:genetics*; D006624:Hippocampus; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000473:pathology
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3