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, 18 (9), 1652-60

Sept5 Deficiency Exerts Pleiotropic Influence on Affective Behaviors and Cognitive Functions in Mice

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Sept5 Deficiency Exerts Pleiotropic Influence on Affective Behaviors and Cognitive Functions in Mice

Go Suzuki et al. Hum Mol Genet.

Abstract

Deletion or duplication of the human chromosome 22q11.2 is associated with many behavioral traits and neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. However, why phenotypes vary widely among individuals with identical deletions or duplications of 22q11.2 and which specific 22q11.2 genes contribute to these phenotypes are still poorly understood. Previous studies have identified a approximately 200 kb 22q11.2 region that contributes to behavioral phenotypes in mice. We tested the role of Septin 5 (Sept5), a gene encoded in the approximately 200 kb region, in affective behaviors, cognitive capacities and motor activity. To evaluate the impact of genetic backgrounds on behavioral phenotypes of Sept5 deficiency, we used mice on two genetic backgrounds. Our data show that Sept5 deficiency decreased affiliative active social interaction, but this phenotypic expression was influenced by genetic backgrounds. In contrast, Sept5 deficiency decreased anxiety-related behavior, increased prepulse inhibition and delayed acquisition of rewarded goal approach, independent of genetic background. These data suggest that Sept5 deficiency exerts pleiotropic effects on a select set of affective behaviors and cognitive processes and that genetic backgrounds could provide an epistatic influence on phenotypic expression.

Figures

Figure 1.
Figure 1.
Active (A) and passive (B) social interactions. Interaction time (mean ± SEM) is shown in two successive 5 min sessions. Asterisks indicate statistically significant differences from WT mice at 1% (**) levels, as determined by Newman–Keuls comparisons. M group: WT–HT, n = 9 pairs; WT–KO, n = 16 pairs. 129E group: WT–HT, n = 14 pairs; WT–KO, n = 12 pairs.
Figure 2.
Figure 2.
Anxiety- and affect-related traits. (A) Elevated plus maze. The relative amount of time (% mean ± SEM) spent in the open arms is shown. Because the homogeneity of variance was violated (Hartley’s F-max = 57.87, P < 0.01), data were transformed using a square root. M group: WT, n = 15; HT, n = 20; KO, n = 22. 129E group: WT, n = 20; HT, n = 26; KO, n = 24. (B) Thigmotaxis. Time (mean ± SEM) spent in the marginal area was measured each 5 min during a 30 min period. M group: WT, n = 18; HT, n = 19; KO, n = 7. 129E group: WT, n = 28; HT, n = 27; KO, n = 25. (C) Immobility in a tail suspension test. Time (mean ± SEM) mice remained immobile is shown. WT, wild-type mice; KO, Sept5 knockout mice. M group: WT, n = 25; HT, n = 33; KO, n = 26. 129E group: WT, n = 28; HT, n = 27; KO, n = 25.
Figure 3.
Figure 3.
Startle (A) and PPI (B). The magnitude of a startle response and the percentage of PPI are plotted against pulse stimuli (75–120 dB) and prepulse stimuli at 4, 8, 12 and 16 dB (69, 73, 77 and 81 dB presented with the 65 dB background noise), respectively. Data are presented as mean ± SEM. M group: WT, n = 20; HT, n = 25; KO, n = 16. 129E group: WT, n = 28; HT, n = 27; KO, n = 25.
Figure 4.
Figure 4.
(A) Rewarded approach. Time (mean ± SEM) spent to reach a rewarded goal in the L-maze is shown. M group: WT, n = 19; HT, n = 32; KO, n = 17. 129E group: WT, n = 23; HT, n = 36; KO, n = 18. (B) Spontaneous alternation. All genotypes show a tendency to alternate an arm to visit upon repeated testing (i.e. >50%). M group: WT, n = 22; HT, n = 23; KO, n = 22. 129E group: WT, n = 28; HT, n = 27; KO, n = 25. (C) Rewarded alternation. M group: WT, n = 13; HT, n = 19; KO, n = 9. 129E group: WT, n = 15; HT, n = 27; KO, n = 16.
Figure 5.
Figure 5.
Spontaneous locomotor activity in an inescapable open field. Distance traveled (mean ± SEM) was measured for 30 min. Each tick on the x-axis represents a 5 min bin. WT, wild-type mice; KO, Sept5 knockout mice. M group: WT, n = 18; HT, n = 19; KO, n = 7. 129E group: WT, n = 28; HT, n = 27; KO, n = 25.

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