Mice lacking alpha1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors.
The 3-fucosyl-N-acetyllactosamine [Lewis x (Le(x)), CD15, SSEA-1] carbohydrate structure is expressed on several glycolipids, glycoproteins, and proteoglycans of the nervous system and has been implicated in cell-cell recognition, neurite outgrowth, and neuronal migration during development. To characterize the functional role of Le(x) carbohydrate structure in vivo, we have generated mutant mice that lack alpha1,3-fucosyltransferase IX (Fut9(-/-)). Fut9(-/-) mice were unable to synthesize the Le(x) structure carried on glycoproteins and glycolipids in embryonic and adult brain. However, no obvious pathological differences between wild-type and Fut9(-/-) mice were found in brain. In behavioral tests, Fut9(-/-) mice exhibited increased anxiety-like responses in dark-light preference and in elevated plus maze tests. Immunohistochemical analysis showed that the number of calbindin-positive neurons was decreased in the basolateral amygdala in Fut9(-/-) mice. These observations indicated that the carbohydrates synthesized by Fut9 play critical roles in functional regulations of interneurons in the amygdalar subdivisions and suggested a role for the Le(x) structure in some aspects of emotional behavior in mice.
Kudo
Takashi
T
Glycogene Function Team, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Central-2, Open Space Laboratory, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
Fujii
Takashi
T
Ikegami
Shiro
S
Inokuchi
Kaoru
K
Takayama
Yuko
Y
Ikehara
Yuzuru
Y
Nishihara
Shoko
S
Togayachi
Akira
A
Takahashi
Satoru
S
Tachibana
Kouichi
K
Yuasa
Shigeki
S
Narimatsu
Hisashi
H
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D064026:Calbindins; D002241:Carbohydrates / Q000032:analysis; D004622:Embryo, Mammalian; D005647:Fucosyltransferases / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006017:Glycolipids / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D007858:Learning; D016256:Lewis X Antigen / Q000032:analysis*; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064026:Calbindins; D002241:Carbohydrates; D006017:Glycolipids; D006023:Glycoproteins; D016256:Lewis X Antigen; D064030:S100 Calcium Binding Protein G; D005647:Fucosyltransferases; C518194:fucosyltransferase 9, mouse