Mice lacking α1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors
Mice lacking α1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors
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DOI：
10.1093/glycob/cwl047
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发表时间：
2007-01-01
期刊：
影响因子：
4.3
通讯作者：
Narimatsu, Hisashi
中科院分区：
文献类型：
--
作者：
Kudo, Takashi;Fujii, Takashi;Narimatsu, Hisashi
3-岩藻糖基-N-乙酰乳糖胺[刘易斯x（Le（x）），CD 15，SSEA-1]碳水化合物结构在神经系统的几种糖脂、糖蛋白和蛋白聚糖上表达，并与发育期间的细胞-细胞识别、神经突生长和神经元迁移有关。为了表征Le（x）碳水化合物结构在体内的功能作用，我们产生了缺乏α 1，3-岩藻糖基转移酶IX（Fut 9（-/-））的突变小鼠。Fut 9（-/-）小鼠不能合成胚胎和成年脑中糖蛋白和糖脂上携带的Le（x）结构。然而，野生型和Fut 9（-/-）小鼠之间的脑组织没有发现明显的病理学差异。在行为测试中，Fut 9（-/-）小鼠在暗-光偏好和高架十字迷宫测试中表现出增加的焦虑样反应。免疫组化结果显示，Fut 9（-/-）小鼠杏仁核基底外侧区钙结合蛋白阳性神经元数量减少。这些观察结果表明，Fut 9合成的碳水化合物在杏仁核分区的中间神经元的功能调节中发挥关键作用，并表明Le（x）结构在小鼠情绪行为的某些方面发挥作用。
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 alpha 1,3-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.