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.

中文翻译：

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鸟嘌呤核苷酸交换因子Spata13影响社会行为和夜间活动。

精子发生相关蛋白13（Spata13）是一种鸟嘌呤核苷酸交换因子（GEF），富含成年人的离散脑区域，在延伸的中央杏仁核（CeA）中有明显的表达。Spata13的丧失，也被称为腺瘤性息肉病交换因子Asef2，尽管可以减少Apc（Min / +）小鼠肠道肿瘤的数量和大小，但没有可识别的表型。然而，尚未研究其与大脑有关的功能。为此，我们使用CRISPR介导的含有GTPase结构域的外显子的CRISPR介导缺失，生成了Spata13基因敲除小鼠品系，GTPase结构域是多种亚型共有的。纯合突变体是可行的，并显示正常。我们对男性和女性队列进行了全面的行为测试，旨在研究与CeA相关的特定功能。在这里，我们显示Spata13通过从属于野生型对照的纯合突变体来调节社会行为。此外，雌性纯合子在明暗循环的黑暗阶段在家庭笼中显示出增加的活性。总之，Spata13除了影响雌性的自愿活动外，还调节雄性和雌性小鼠的社会等级。