The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-Terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR ( "C-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on "C-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The "C-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in "C-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between "C-KI and wild-Type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that "C-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.
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