Objective To investigate the effect of the monoamine oxidase A (MAOA), Maoa c.1409 T > C synonymous mutation on anxiety, fear, and other emotional behaviors in mice. Methods In this study, CRISPR/Cas9 technology was used to construct a mouse model of a single nucleotide polymorphism (SNP) synonymous mutation. We evaluated the differential effect of this gene between males and females through animal behavior and gene expression studies in animal models. In terms of animal behavior, an open field test, elevated plus maze test, defensive burial experiment, forced swimming test, and 3D behavioral analysis were used. Other method were used to evaluate behavioral differences between male and female mice with polymorphisms in Maoa synonymous mutant genes. Results The result of the open field experiment showed that the residence time of female SNP mice in the central area was significantly higher than that of male SNP mice (P<0.001). In the elevated cross maze experiment, the EPM result showed that the time and frequency of male SNP mice entering the open arm were higher than those of female SNP mice, but there was no significant difference. The defensive burial test showed that the number and duration of excavations by female SNP mice in response to rat urine were significantly reduced (P<0.01). The FST showed that SNP females had shorter immobility time and longer swimming time (P<0.05), and thus their depression was lower than males. 3D-AI fine behavior analysis showed no significant male and female differences, except for the movement trajectory and climbing behavior of mice. The MAOA enzyme content of female SNP mice was significantly lower than that of male SNP mice (P<0.001), but there was no significant difference in enzyme activity between male and female SNP mice. Conclusions The synonymous mutation of Maoa c.1409 T > C acts by affecting the expression of MAOA and may have different fear, anxiety, and mood effects in male and female SNP mice.