Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

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 (Delta C-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on Delta C-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The Delta C-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in Delta 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 Delta C-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that Delta C-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.