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.
Highlights
Spermatogenesis-associated protein 13 (Spata13, ID 219140) codes for an eponymous protein acting as a guanine nucleotide exchange factor (GEF) for RhoA, Rac1 and Cdc42 GTPases (Kawasaki et al 2007; Bristow et al 2009)
Analysis of the data produced in these tests found no effect of genotype in any of the parameters analysed, suggesting that loss of Spata13 did not result in gross changes in these behaviours (Table 1)
The loss of Spata13 did not affect the number of spines per μm in the prefrontal cortex (Welch’s t test, p = 0.9667, n = 4 for each genotype), (Fig. 1)
Summary
Spermatogenesis-associated protein 13 (Spata, ID 219140) codes for an eponymous protein acting as a guanine nucleotide exchange factor (GEF) for RhoA, Rac and Cdc GTPases (Kawasaki et al 2007; Bristow et al 2009). Spata is expressed in discrete loci within the brain (Lein et al 2007) with particular enrichment in the central extended amygdala (Becker et al 2008). The central extended amygdala and the central amygdala have been well characterised. The regions have been shown to play important roles in anxiety-like, fear and threat (Shackman and Fox 2016; Fox and Shackman 2017), pain (Bourbia et al 2010), feeding, reward and addiction (Koob 1999; Waraczynski 2006; Douglass et al 2017), voluntary activity (Izumo et al 2012) and aggressive behaviours (Haller 2018)
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