Tetratricopeptide repeat domain 9A knockout induces social anxiety and impairs offense behaviors in female mice

Abstract

Objectives: The involvement of tetratricopeptide repeat domain 9A (TTC9A) in anxiety-like behaviors through estrogen action has been reported in female mice, this study further investigated its effects on social anxiety and aggressive behaviors.

Materials and smethods: Using female Ttc9a knockout (Ttc9a-/-) mice, the role of TTC9A in anxiety was investigated in non-social and social environments through home-cage emergence and social interaction tests, respectively, whereas aggressive behaviors were examined under the female intruder test.

Results: We observed significant social behavioral deficits with pronounced social and non-social anxiogenic phenotypes in female Ttc9a-/- mice. When tested for aggressive-like behaviors, we found a reduction in offense in Ttc9a-/- animals, suggesting that TTC9A deficiency impairs the offense responses in female mice.

Conclusion: Future study investigating mechanisms underlying the social anxiety-like behavioral changes in Ttc9a-/- mice may promote the understanding of social and anxiety disorders.

Keywords: Aggression; Anxiety; Behavioral tests; Social behavior; Tetratricopeptide repeat - domain 9A (TTC9A).

Figure 1

Ttc9a-/- female mice show anxiogenic-like behavior and deficits in social behavior. (a) A schematic diagram represents the timeline of the experimental design. (b) Graphical representation of the home-cage apparatus used in the home-cage emergence test. (c) Ttc9a-/- female mice showed anxiogenic-like behavior with a significantly increased escape latency in the home-cage emergence test. (d) Ttc9a-/- female mice showed deficits in the social interaction test, with increased non-social exploration and decreased social exploration. Behavioral categories of which both groups showed less than 5% total time are collapsed into the ‘Others’ sector, including move towards, move away, freeze, and defensive upright posture. Data are presented as mean + SEM, * represents P<0.05, ** represents P≤0.01, *** represents P≤0.001, independent samples t-test or Mann Whitney U-test as appropriate

Figure 2

Ttc9a-/- female mice show impaired offense behaviors compared with wild-type. (a) Ttc9a-/- female mice showed no significant difference in attack latency in the female intruder test compared with wild-type mice. (b) Ttc9a-/- female mice showed an increase in non-social exploration and decrease in total offense score, social exploration, and move towards behaviors. Data are presented as mean + SEM, * represents P<0.05, ** represents P≤0.01, independent samples t-test or Mann Whitney U-test as appropriate