ArticleMolecular reproduction and development2015
Role of human Na,K-ATPase alpha 4 in sperm function, derived from studies in transgenic mice.
Article in Molecular reproduction and development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- The Sperm Acrosomal Reaction Depends on the Function of Both Na,K-ATPase α1 and α4 Isoforms.International journal of molecular sciences · 2026Article
- Alpha4 Na,K-ATPase Localization and Expression Are Dynamic Aspects of Spermatogenesis and in Sperm Incubated Under Capacitating Conditions.International journal of molecular sciences · 2025Article
- Novel mouse model of alternating hemiplegia of childhood exhibits prominent motor and seizure phenotypes.Neurobiology of disease · 2024Article
- Possible mechanisms involved in the protective effect of lutein against cyclosporine-induced testicular damage in rats.Heliyon · 2024Article
- The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function.International journal of molecular sciences · 2023Review
- The Non-Gastric HInternational journal of molecular sciences · 2022Article
- Na,K-ATPase α4, and Not Na,K-ATPase α1, is the Main Contributor to Sperm Motility, But its High Ouabain Binding Affinity Site is Not Required for Male Fertility in Mice.The Journal of membrane biology · 2021Article
- Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.The Journal of clinical endocrinology and metabolism · 2021Review
- Sperm ion channels and transporters in male fertility and infertility.Nature reviews. Urology · 2021Review
- Design, Synthesis, and in Vitro and in Vivo Evaluation of Ouabain Analogues as Potent and Selective Na,K-ATPase α4 Isoform Inhibitors for Male Contraception.Journal of medicinal chemistry · 2018Article
- Molecular Basis of Human Sperm Capacitation.Frontiers in cell and developmental biology · 2018Review
- Signaling mechanisms in mammalian sperm motility.Biology of reproduction · 2017Review
- The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease.Frontiers in physiology · 2017Review
- Pipeline for contraceptive development.Fertility and sterility · 2016Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Most of our knowledge on the biological role of the testis-specific Na,K-ATPase alpha 4 isoform derives from studies performed in non-human species. Here, we studied the function of human Na,K-ATPase alpha 4 after its expression in transgenic mice. Using a bacterial artificial chromosome (BAC) construct containing the human ATP1A4 gene locus, we obtained expression of the human α4 transgene specifically in mouse sperm testis and, in the sperm flagellum. The expressed human alpha 4 was active, and compared to wild-type sperm, those from transgenic mice displayed higher Na,K-ATPase alpha 4 activity and greater binding of fluorescently labeled ouabain, which is typical of the alpha 4 isoform. The expression and activity of endogenous alpha 4 and the other Na,K-ATPase alpha isoform present in sperm, alpha 1, remained unchanged. Male mice expressing the human ATP1A4 transgene exhibited similar testis size and morphology, normal sperm number and shape, and no changes in overall fertility compared to wild-type mice. Sperm carrying the human transgene exhibited enhanced total motility and an increase in multiple parameters of sperm movement, including higher sperm hyperactive motility. In contrast, no statistically significant changes in sperm membrane potential, protein tyrosine phosphorylation, or spontaneous acrosome reaction were found between wild-type and transgenic mice. Altogether, these results provide new genetic evidence for an important role of human Na,K-ATPase alpha 4 in sperm motility and hyperactivation, and establishes a new animal model for future studies of this isoform.
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