ArticleProceedings of the National Academy of Sciences of the United States of America1997
Impaired fertility in mice deficient for the testicular germ-cell protease PC4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 156 citations in OpenAlex.
- Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- TMPRSS12 Functions in Meiosis and Spermiogenesis and Is Required for Male Fertility in Mice.Frontiers in cell and developmental biology · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response.Frontiers in immunology · 2021Review
- Tmprss12 is required for sperm motility and uterotubal junction migration in mice†.Biology of reproduction · 2020Article
- Duplications in 19p13.3 are associated with male infertility.Journal of assisted reproduction and genetics · 2019Article
- Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- The Acrosomal Matrix.Advances in anatomy, embryology, and cell biology · 2016Review
- Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).The Journal of biological chemistry · 2013Article
- Genetics of the first seven proprotein convertase enzymes in health and disease.Current genomics · 2013Article
- Phospholipase B is activated in response to sterol removal and stimulates acrosome exocytosis in murine sperm.The Journal of biological chemistry · 2013Article
- Proprotein convertase furin regulates apoptosis and proliferation of granulosa cells in the rat ovary.PloS one · 2013Article
- Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice.Molecular human reproduction · 2012Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
- Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion.The Journal of biological chemistry · 2012Article
- The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction.The Journal of biological chemistry · 2011Article
- The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone.Molecular and cellular biochemistry · 2011Article
- Mouse models in male fertility research.Asian journal of andrology · 2011Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PC4 is a member of the proprotein convertase family of serine proteases implicated in the processing of a variety of polypeptides including prohormones, proneuropeptides, and cell surface proteins. In rodents, PC4 transcripts have been detected in spermatocytes and round spermatids exclusively, suggesting a reproductive function for this enzyme. In an effort to elucidate this function, we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem cells and have produced mice carrying the mutation. In intercrosses of heterozygous mutant mice, there was low transmission of the mutant Pcsk4 allele to the progeny, resulting in lower than expected incidence of heterozygosity and null homozygosity. The in vivo fertility of homozygous mutant males was severely impaired in the absence of any evident spermatogenic abnormality. In vitro, the fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly reduced. Moreover, eggs fertilized by these spermatozoa failed to grow to the blastocyst stage. These results suggest that PC4 in the male may be important for achieving fertilization and for supporting early embryonic development in mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.