The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity

Abstract

Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a Spata13 knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that Spata13 modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light-dark cycle. In summary, Spata13 modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.

Fig. 1

Spine counts in female prefrontal cortex. Spine counts per µm of prefrontal cortex slices do not show differences between female WT and HOM Spata13 mice

Fig. 2

Spata13 KO mice are subordinate to the dominant WT mice. Assessment of dominant/subordinate status using the social dominance tube test shows that female and male WT mice won more challenges when paired against HOM Spata13 mice. *p < 0.05, **p < 0.01

Fig. 3

Home-cage activity in Spata13 females. Analysis of home-cage activity over time in female animals shows that Spata13 knockout animals show elevated activity levels in the dark phase of the light–dark cycle (a). No observable differences in activity were observed in female animals upon their release into constant darkness (b)

Fig. 4

Home cage activity in Spata13 males. Analysis of home-cage activity over time in male animals shows that Spata13 knockout animals show no differences in activity levels in either the light–dark cycle (a) or upon release into constant darkness (b)