Knockout of mouse receptor accessory protein 6 leads to sperm function and morphology defects
| Autor: | Kaori Nozawa, Qingnan Liang, Rui Chen, Darius J Devlin, Smriti Agrawal Zaneveld, Xiao Han, Jacob Michael Harnish, Martin M. Matzuk, Abigail R. Moye |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Retinal degeneration
Male endocrine system Spermiogenesis Motility Biology Mice medicine Animals RNA Messenger Zona pellucida Eye Proteins Sperm motility reproductive and urinary physiology Infertility Male Mice Knockout urogenital system Endoplasmic reticulum Membrane Proteins Cell Biology General Medicine medicine.disease Epididymis Spermatozoa Cell biology medicine.anatomical_structure Reproductive Medicine Gene Expression Regulation Mutation Spermatogenesis Research Article |
| Zdroj: | Biol Reprod |
| Popis: | Receptor accessory protein 6 (REEP6) is a member of the REEP/Ypt-interacting protein family that we recently identified as essential for normal endoplasmic reticulum homeostasis and protein trafficking in the retina of mice and humans. Interestingly, in addition to the loss of REEP6 in our knockout (KO) mouse model recapitulating the retinal degeneration of humans with REEP6 mutations causing retinitis pigmentosa (RP), we also found that male mice are sterile. Herein, we characterize the infertility caused by loss of Reep6. Expression of both Reep6 mRNA transcripts is present in the testis; however, isoform 1 becomes overexpressed during spermiogenesis. In vitro fertilization assays reveal that Reep6 KO spermatozoa are able to bind the zona pellucida but are only able to fertilize oocytes lacking the zona pellucida. Although spermatogenesis appears normal in KO mice, cauda epididymal spermatozoa have severe motility defects and variable morphological abnormalities, including bent or absent tails. Immunofluorescent staining reveals that REEP6 expression first appears in stage IV tubules within step 15 spermatids, and REEP6 localizes to the connecting piece, midpiece, and annulus of mature spermatozoa. These data reveal an important role for REEP6 in sperm motility and morphology and is the first reported function for a REEP protein in reproductive processes. Additionally, this work identifies a new gene potentially responsible for human infertility and has implications for patients with RP harboring mutations in REEP6. |
| Databáze: | OpenAIRE |
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