Mutations in S-phase cyclin A-associated protein in the endoplasmic reticulum (SCAPER) cause a recessively inherited multisystemic disorder whose main features are retinal degeneration and intellectual disability. SCAPER, originally identified as a cell cycle regulator, was also suggested to be a ciliary protein. Because Scaper mutant males are sterile, we set up to characterize their phenotype. The testes of Scaper mutant mice are significantly smaller than those of WT mice. Histology revealed no signs of spermatogenesis, and seminiferous tubules contained mainly Sertoli cells with a few spermatogonia/spermatogonial stem cells (SSCs). In WT testes, SCAPER is expressed by SSCs and in the various stages of spermatogenesis, as well as in Sertoli cells. In WT spermatozoa SCAPER is not expressed in the flagellum but rather in the head compartment, where it is found both in the nucleus and in the perinuclear region. Scaper mutant females present reduced fertility, manifested by a significantly smaller litter size compared to WT females. Mutant ovaries are similar in size but comprised of significantly less primordial and antral follicles, compared to WT ovaries, while the number of atretic follicles is significantly higher. In WT ovarian follicles SCAPER is expressed in the somatic granulosa cells as well as in the oocyte. In conclusion, our data demonstrate that SCAPER is a crucial component in both male and female reproductive systems. We hypothesize that the reproductive phenotype observed in Scaper mutant mice is rooted in SCAPER’s interaction with cyclin A/Cdk2, which play an important role, however different, in male and female gonads.

中文翻译：

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SCAPER 缺陷小鼠的雄性不育和雌性生育能力降低。

内质网 (SCAPER) 中 S 期细胞周期蛋白 A 相关蛋白的突变导致隐性遗传的多系统疾病，其主要特征是视网膜变性和智力障碍。SCAPER 最初被确定为细胞周期调节剂，也被认为是一种纤毛蛋白。因为Scaper突变雄性是不育的，我们设置来表征它们的表型。Scaper的睾丸突变小鼠明显小于 WT 小鼠。组织学显示没有精子发生的迹象，生精小管主要含有支持细胞和少量精原细胞/精原干细胞 (SSC)。在 WT 睾丸中，SCAPER 由 SSC 和在精子发生的各个阶段以及支持细胞中表达。在 WT 精子中，SCAPER 不在鞭毛中表达，而是在头部隔室中表达，在细胞核和核周区域中都可以找到它。斯卡普突变雌性表现出生育力降低，与 WT 雌性相比，产仔数明显减少。与 WT 卵巢相比，突变卵巢的大小相似，但由明显较少的原始卵泡和窦卵泡组成，而闭锁卵泡的数量则显着增加。在 WT 卵泡中，SCAPER 在体细胞颗粒细胞和卵母细胞中表达。总之，我们的数据表明 SCAPER 是男性和女性生殖系统的重要组成部分。我们假设在Scaper突变小鼠中观察到的生殖表型源于 SCAPER 与细胞周期蛋白 A/Cdk2 的相互作用，后者在雄性和雌性性腺中发挥重要作用，但又有所不同。