P11 Loss-of-Function is Associated with Decreased Cell Proliferation and Neurobehavioral Disorders in Mice.

Although depression is associated with anxiety and memory deficit in humans, the molecular mechanisms of the complication remain largely unknown. In this study, we generated knockout mice using CRISPR/Cas9 technology, as well as knockout MEF cell lines, and confirmed depression-like phenotype. We observed that knockout of in MEFs led to a decreased cell proliferation compared with MEFs. Moreover, knockout resulted in a larger cell size, which resulted probably from accumulated F-actin stress fibers. The number of proliferating cells was decreased in the hippocampus of KO mice. We observed anxiety-like disorder in addition to depression phenotype in the knockout mice. In addition, knockout of led to memory deficit in female mice, but not in males. These data indicated that P11 is involved in regulating cell proliferation and cell size. The molecular associations of depression behavior with anxiety and memory deficit suggested a potential approach to improve therapeutic intervention through P11 in these disorders.