Mice deficient in collapsin response mediator protein-1 exhibit impaired long-term potentiation and impaired spatial learning and memory.
Collapsing response mediator protein-1 (CRMP-1) was initially identified in brain and has been implicated in plexin-dependent neuronal function. The high amino acid sequence identity among the five CRMPs has hindered determination of the functions of each individual CRMP. We generated viable and fertile CRMP-1 knock-out (CRMP-1(-/-)) mice with no evidence of gross abnormality in the major organs. CRMP-1(-/-) mice exhibited intense microtubule-associated protein 2 (MAP2) staining in the proximal portion of the dendrites, but reduced and disorganized MAP2 staining in the distal dendrites of hippocampal CA1 pyramidal cells. Immunoreactivity to GAP-43 (growth-associated protein-43) and PSD95 (postsynaptic density-95) (a postsynaptic membrane adherent cytoskeletal protein) was also decreased in the CA1 region of the knock-out mice. These changes were consistent with the mutant mice showing a reduction in long-term potentiation (LTP) in the CA1 region and impaired performance in hippocampal-dependent spatial learning and memory tests. CRMP-1(-/-) mice showed a normal synapsin I labeling pattern in CA1 and normal paired-pulse facilitation. These findings provide the first evidence suggesting that CRMP-1 may be involved in proper neurite outgrowth in the adult hippocampus and that loss of CRMP-1 may affect LTP maintenance and spatial learning and memory.
Su
Kang-Yi
KY
Institute of Molecular Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Chien
Wei-Lin
WL
Fu
Wen-Mei
WM
Yu
I-Shing
IS
Huang
Hsiang-Po
HP
Huang
Pei-Hsing
PH
Lin
Shu-Rung
SR
Shih
Jin-Yuan
JY
Lin
Yi-Ling
YL
Hsueh
Yi-Ping
YP
Yang
Pan-Chyr
PC
Lin
Shu-Wha
SW
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D019922:GAP-43 Protein / Q000378:metabolism; D051528:Guanylate Kinases; D006624:Hippocampus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D013550:Swimming; D000098855:Collapsin Response Mediator Protein 1
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000098855:Collapsin Response Mediator Protein 1; D051528:Guanylate Kinases