Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning.
The HNK-1 carbohydrate epitope, a sulfated glucuronic acid at the non-reducing terminus of glycans, is expressed characteristically on a series of cell adhesion molecules and is synthesized through a key enzyme, glucuronyltransferase (GlcAT-P). We generated mice with a targeted deletion of the GlcAT-P gene. The GlcAT-P -/- mice exhibited normal development of gross anatomical features, but the adult mutant mice exhibited reduced long term potentiation at the Schaffer collateral-CA1 synapses and a defect in spatial memory formation. This is the first evidence that the loss of a single non-reducing terminal carbohydrate residue attenuates brain higher functions.
Yamamoto
Shoji
S
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology) Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Oka
Shogo
S
Inoue
Mitsuhiro
M
Shimuta
Misa
M
Manabe
Toshiya
T
Takahashi
Hideki
H
Miyamoto
Masaomi
M
Asano
Masahide
M
Sakagami
Junko
J
Sudo
Katsuko
K
Iwakura
Yoichiro
Y
Ono
Katsuhiko
K
Kawasaki
Toshisuke
T
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D018959:CD57 Antigens / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D004594:Electrophysiology; D000939:Epitopes; D017353:Gene Deletion; D006017:Glycolipids / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D007858:Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009420:Nervous System / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D018959:CD57 Antigens; D002241:Carbohydrates; D000939:Epitopes; D006017:Glycolipids; D006023:Glycoproteins