Disruption of Ssp411 causes impaired sperm head formation and male sterility in mice
Disruption of Ssp411 causes impaired sperm head formation and male sterility in mice
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Ssp411 的破坏导致小鼠精子头形成受损和雄性不育
DOI：
10.1016/j.bbagen.2017.12.005
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发表时间：
2018-03-01
影响因子：
3
通讯作者：
Shi, Huijuan
中科院分区：
文献类型：
--
作者：
Liu, Miao;Ru, Yanfei;Shi, Huijuan
背景：我们先前克隆了Ssp 411基因。我们发现，Ssp 411蛋白主要表达在大鼠睾丸中的精子细胞中的一个阶段依赖性的方式。虽然我们的研究结果强烈表明，Ssp 411可能在哺乳动物精子发生中发挥重要作用，这一假设还没有studyed.Methods：我们首先使用实时PCR，Western blotting和免疫组化证实，Ssp 411在几个小鼠组织中的表达模式是类似的，其在相应的大鼠组织中的表达模式。为了更好地理解Ssp 411在体内雄性生殖中的作用，我们鉴定并表征了通过piggyBac（PB）转座子插入产生的Ssp 411表达破坏的鼠品系（Ssp 411（PB/PB））。结果：Ssp 411 mRNA和蛋白质均在睾丸精子发生第9步后的精子细胞中表达，但在第9步后的精子细胞中表达量最高。表型分析表明，只有Ssp 411（PB/PB）雄性不育。这些男性的睾丸较小，精子数量减少，精子活力降低和精子畸形。显微镜分析表明，在Ssp 411（PB/PB）精子细胞中，一种结构重塑的精子头部是异常的。蛋白质组芯片分析和GST pull-down分析结果表明，Ssp 411通过与PSMC 3相互作用参与了泛素-蛋白酶体系统。据报道，这是manchette相关的和重要的精子细胞的头部shapingofspermatids.Conclusions：我们的研究表明，Ssp 411是所需的精子发生。它似乎在精子头部成形中起作用。Ssp 411基因缺失可导致精子畸形并导致男性不育。一般意义：Ssp 411（PB/PB）小鼠品系是特发性少弱畸形精子症（iOAT）的动物模型，该基因可能成为iOAT患者的治疗靶点。
Background: We previously cloned the Ssp411 gene. We found that the Ssp411 protein is predominantly expressed in elongated spermatids in the rat testis in a stage-dependent manner. Although our findings strongly suggested that Ssp411 might play an important role in mammalian spermatogenesis, this hypothesis has not been studied.Methods: We first used real-time PCR, Western blotting and immunohistochemistry to confirm that the expression pattern of Ssp411 in several murine tissues is similar to its expression pattern in corresponding rat tissues. To better understand the roles of Ssp411 in male reproduction in vivo, we identified and characterized an Ssp411 expression-disrupted murine strain (Ssp411(PB/PB)) that was generated by piggyBac (PB) transposon insertion. We studied Ssp411-interacting proteins using proteome microarray, co-IP and GST pull-down assay.Results: Both Ssp411 mRNA and protein were detected exclusively in spermatids after step 9 during spermiogenesis in testis. Phenotypic analysis suggested that only Ssp411(PB/PB) males are sterile. These males have smaller testes, reduced sperm counts, decreased sperm motility and deformed spermatozoa. Microscopy analysis indicated that the manchette, a structurally reshaped sperm head, is aberrant in Ssp411(PB/PB) spermatids. The results of proteome microarray analysis and GST pull-down assays suggested that Ssp411 participates the ubiquitin-proteasome system by interacting with PSMC3. This has been reported to be manchette-associated and important for the head shaping of spermatids.Conclusions: Our study suggested that Ssp411 is required for spermiogenesis. It seems to play a role in sperm head shaping. The lack of Ssp411 causes sperm deformation and results in male infertility.General significance: Ssp411(PB/PB) mouse strain is an animal model of idiopathic oligoasthenoteratozoospermia (iOAT), and the gene may represent a therapeutic target for iOAT patients.