ArticlePLoS genetics2020
Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 31 citations in OpenAlex.
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- Bioinformatics and multi-omics approaches in male infertility: implications for diagnosis and assisted reproduction.Journal of assisted reproduction and genetics · 2026Review
- Biallelic variants in TBC1D8 are potentially associated with male infertility due to non-obstructive azoospermia or cryptozoospermia.Asian journal of andrology · 2026Article
- Sperm mitochondrial sheath formation - how and why?Nature reviews. Urology · 2026Review
- HomozygousTranslational andrology and urology · 2026Article
- Human teratozoospermia-related AGTPBP1 R791H mutation is associated with sperm head and tail defects in a CRISPR-engineered murine model.Journal of assisted reproduction and genetics · 2026Article
- Of mice and men: translating mouse knockout models of human male infertility.Reproduction (Cambridge, England) · 2025Review
- Disruption of TEX38 impairs sperm morphogenesis and the migration of sperm into the oviduct.Communications biology · 2025Article
- A novel mechanism of sperm midpiece epididymal maturation and the role of CCDC112 in sperm midpiece formation and establishing an optimal flagella waveform.Cell communication and signaling : CCS · 2025Article
- Extant and extinct bilby genomes combined with Indigenous knowledge improve conservation of a unique Australian marsupial.Nature ecology & evolution · 2024Article
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- Decreased Klotho Expression Causes Accelerated Decline of Male Fecundity through Oxidative Injury in Murine Testis.Antioxidants (Basel, Switzerland) · 2023Article
- ADAD2 functions in spermiogenesis and piRNA biogenesis in mice.Andrology · 2023Article
- Localization Patterns of RAB3C Are Associated with Murine and Human Sperm Formation.Medicina (Kaunas, Lithuania) · 2022Article
- In Silico Identification of lncRNAs Regulating Sperm Motility in the Turkey (International journal of molecular sciences · 2022Article
- Mitochondrial regulation during male germ cell development.Cellular and molecular life sciences : CMLS · 2022Review
- The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy modelFrontiers in molecular neuroscience · 2022Article
- ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular basis of the morphogenesis of sperm head and tail in mice.Reproductive medicine and biologyReview
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 2-15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. The mitochondria of the sperm-tail had an abnormal irregular arrangement, abnormal diameter, and structural defects. Moreover, the axoneme structure of sperm tails was severely disturbed. Several TBC1D21 interactors were selected via proteomic analysis and functional grouping. Two of the candidate interactors, a subunit protein of translocase in the outer membrane of mitochondria (TOMM20) and an inner arm component of the sperm tail axoneme (Dynein Heavy chain 7, DNAH7), confirmed in vivo physical co-localization with TBC1D21. In addition, TOMM20 and DNAH7 detached and dispersed outside the axoneme in Tbc1d21-deficient sperm, instead of aligning with the axoneme. From a clinical perspective, the transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia. We concluded that TBC1D21 is critical for mitochondrial and axoneme development of mammalian sperm.
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