Mice lacking α1,3-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 α1,3-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.