Deletion of a seminal gene cluster reinforces a crucial role of SVS2 in male fertility

Miyuki Shindo, Masafumi Inui, Woojin Kang, Moe Tamano, Cai Tingwei, Shuji Takada, Taku Hibino, Manabu Yoshida, Kaoru Yoshida, Hiroshi Okada, Teruaki Iwamoto, Kenji Miyado, Natsuko Kawano

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Multiple genes, whose functions or expression are overlapping, compensate for the loss of one gene. A gene cluster in the mouse genome encodes five seminal vesicle proteins (SVS2, SVS3, SVS4, SVS5, and SVS6). These proteins are produced by male rodents and function in formation of the copulatory plug following mating. SVS2 plays an essential role in the successful internal fertilization by protecting the sperm membrane against a uterine immune attack. We hypothesized that the four remaining seminal vesicle proteins (SVPs) of this gene cluster may partially/completely compensate for the deficiency of SVS2. For confirming our hypothesis, we generated mice lacking the entire SVP-encoding gene cluster and compared their fecundity with Svs2-deficient (Svs2-/-) mice; that is, mice deficient in Svs2 alone. A single loxP site remained after the deletion of the Svs2 gene. Therefore, we inserted another loxP site by combining the CRISPR/Cas9 system with single-stranded oligodeoxynucleotides (ssODN). Male mice lacking the entire SVP-encoding gene cluster (Svs2-6-/- mice) and thereby all five SVP proteins, generated by the deletion of 100kbp genomic DNA, showed low fecundity. However, the fecundity level was comparable with that from Svs2-/- male mice. Our results demonstrate that SVS3, SVS4, SVS5, and SVS6 do not function in the protection of sperm against a uterine immune attack in the absence of SVS2. Thus, Svs2 is the critical gene in the SVP gene cluster.

Original languageEnglish
Article number4557
JournalInternational Journal of Molecular Sciences
Volume20
Issue number18
DOIs
Publication statusPublished - 2 Sep 2019

Keywords

  • Deletion
  • Gene cluster
  • Male fertility
  • Semen
  • Seminal vesicle proteins

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