Abi3bp was originally discovered as Abi3-Src homology 3 (SH3) binding protein and has been proved to have a broad expression profile in adult tissues. Although previous studies have indicated that Abi3bp may be associated with cancer suppression, cell senescence, dendritic refinement and mental disorder, most conclusions achieved were based on in vitro model or genome-wide association study. In this work, we constructed an Abi3bp-deficient mouse model and observed phenotypic changes. The generated Abi3bp-knockout mice are viable and fertile, develop normally and exhibit no significant differences in anxiety or depression-like behaviors, olfactory function and tumor incidence. These data suggest that the function of Abi3bp in in vitro models does not translate to a similar role in the intact animal. Its depletion may be compensated by other genes, which needs to be addressed in future studies.