Kudo Takashi, Fujii Takashi, Ikegami Shiro, Inokuchi Kaoru, Takayama Yuko, Ikehara Yuzuru, Nishihara Shoko, Togayachi Akira, Takahashi Satoru, Tachibana Kouichi, Yuasa Shigeki, Narimatsu Hisashi
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.
Glycobiology. 2007 Jan;17(1):1-9. doi: 10.1093/glycob/cwl047. Epub 2006 Sep 14.
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.
3-岩藻糖基-N-乙酰乳糖胺[刘易斯x（Le(x)）、CD15、阶段特异性胚胎抗原-1（SSEA-1）]碳水化合物结构在神经系统的多种糖脂、糖蛋白和蛋白聚糖上表达，并与发育过程中的细胞间识别、神经突生长和神经元迁移有关。为了在体内表征Le(x)碳水化合物结构的功能作用，我们培育出了缺乏α1,3-岩藻糖基转移酶IX（Fut9(-/-)）的突变小鼠。Fut9(-/-)小鼠无法合成胚胎期和成年期大脑中糖蛋白和糖脂上携带的Le(x)结构。然而，在大脑中未发现野生型和Fut9(-/-)小鼠之间存在明显的病理差异。在行为测试中，Fut9(-/-)小鼠在明暗偏好和高架十字迷宫测试中表现出焦虑样反应增加。免疫组织化学分析表明，Fut9(-/-)小鼠基底外侧杏仁核中钙结合蛋白阳性神经元的数量减少。这些观察结果表明，Fut9合成的碳水化合物在杏仁核亚区中间神经元的功能调节中起关键作用，并提示Le(x)结构在小鼠情绪行为的某些方面发挥作用。
