However, its mechanisms and potential sex-specific effects remain unclear.<h4>Methods</h4>Behavioral tests were used to assess phenotypes related to depression, anxiety, and learning in male and female wild-type (WT) and Negr1<sup>-/-</sup> mice, and molecular assays were performed to evaluate endoplasmic reticulum (ER) stress and apoptosis in the brain, liver, and colon. The gene discussed is NEGR1; the disease is major depressive disorder.