We previously identified a novel molecule “Shati/Nat8l” from the nucleus accumbens of mice. However, the physiological roles of the SHATI protein are not clear. To investigate the effect of SHATI on the central nervous system and behavior, we studied knockout mice of this protein. We carried out various behavior tests using Shati-knockout mice. Shati-knockout mice did not differ from wild type mice in learning and memory. In the open field test, Shati-knockout mice did not differ from wild-type mice in time of stay in the outer, middle and center areas. On the other hand, Shati-knockout mice showed increases in rearing and grooming time in the open field test, and exploration time of novel objects. These results suggested that knockout of the Shati gene may increase exploration in specific circumstances. Interestingly, the Shati-knockout mice avoided social interaction with unfamiliar mice out of their home cage, although there was no difference in social interaction in their home cage compared with wild type mice. Lack of the Shati gene increased brain-derived neurotrophic factor (BDNF) mRNA in the prefrontal cortex and hippocampus, and decreased glial cell line-derived neurotrophic factor (GDNF) mRNA in the striatum and hippocampus, and lipopolysaccharides-induced TNF-α factor (LITAF) mRNA in the striatum. Since these factors play important roles in behavior, alteration of expression of these factors may be related to the induction of exploration and reduction of social interaction in Shati-knockout mice.