Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain
Author(s) -
Huimin Wang,
Eiji Shimizu,
YaPing Tang,
Min Cho,
Maureen Kyin,
Wenqi Zuo,
D Robinson,
Peter J. Alaimo,
Chao Zhang,
Hiromi Morimoto,
Min Zhuo,
Ruiben Feng,
Kevan M. Shokat,
Joe Z. Tsien
Publication year - 2003
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0636870100
Subject(s) - knockout mouse , consolidation (business) , memory consolidation , conditional gene knockout , calmodulin , neuroscience , microbiology and biotechnology , in vivo , biology , protein engineering , phenotype , genetics , receptor , biochemistry , gene , enzyme , accounting , hippocampus , business
By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout andor manipulation technology. This method is based on the creation of a specific interaction interface between a modified protein domain and sensitized inhibitors. By introducing this system into genetically modified mice, we can readily manipulate the activity of a targeted protein, such as alpha-Ca(2+)calmodulin-dependent protein kinase II (alphaCAMKII), on the time scale of minutes in specific brain subregions of freely behaving mice. With this inducible and region-specific protein knockout technique, we analyzed the temporal stages of memory consolidation process and revealed the first postlearning week as the critical time window during which a precise level of CaMKII reactivation is essential for the consolidation of long-term memories in the brain.
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