α1,6-Fucosyltransferase-deficient Mice Exhibit Multiple Behavioral Abnormalities Associated with a Schizophrenia-like Phenotype

• DOI: 10.1074/jbc.m110.172536
• Publication Date: 2011-04-07T15:30:03Z
• Authors: Tomohiko Fukuda; Hirokazu Hashimoto; Natsumi Okayasu; Akihiko Kameyama; Hiroshi Onogi; Osamu Nakagawasai; Takahiro Nakazawa; Tomoyo Kurosawa; Yan Hao; Tomoya Isaji; Takeshi Tadano; Hisashi Narimatsu; Naoyuki Taniguchi; Jianguo Gu
• Keywords: Fucosyltransferase

Previously, we reported that α1,6-fucosyltransferase (Fut8)-deficient (Fut8−/−) mice exhibit emphysema-like changes in the lung and severe growth retardation due to dysregulation of TGF-β1 EGF receptors abnormal integrin activation, respectively. To study role α1,6-fucosylation brain tissue where Fut8 is highly expressed, examined Fut8−/− using a combination neurological behavioral tests. exhibited multiple abnormalities consistent with schizophrenia-like phenotype. displayed increased locomotion compared wild-type (Fut8+/+) heterozygous (Fut8+/−) mice. In particular, showed strenuous hopping behavior novel environment. Working memory performance was impaired as evidenced by Y-maze Furthermore, prepulse inhibition (PPI) deficiency. Intriguingly, although there no significant difference between Fut8+/+ Fut8+/− PPI test under normal conditions, after exposure restraint stress. This result suggests reduced expression plausible cause schizophrenia related disorders. The levels serotonin metabolites were significantly decreased both striatum nucleus accumbens Likewise, treatment haloperidol, which an antipsychotic drug antagonizes dopaminergic serotonergic receptors, behaviors. present first clearly demonstrate plays important brain, it might be Thus, results provide new insights into underlying mechanisms responsible for