In this study, diffusion tensor imaging (DTI) and resting-state functional MRI were employed on a depression knock-out mouse model, which shows behaviors of anxiety and depression. The brain network hubs were investigated by region-of-interest (ROI) and connectivity analyses. Our results showed altered resting-state connectivity in prefrontal and hippocampal areas. Also, altered DTI indices were also found in thalamus and hippocampus. These findings are consistent with previous human studies and suggest the brain neuroimaging could be potentially useful to reveal the brain network hubs affected by depression on the proposed mouse model.