ArticleThe Journal of biological chemistry2011
Impaired spermatogenesis and fertility in mice carrying a mutation in the Spink2 gene expressed predominantly in testes.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Current Update on Categorization of Migraine Subtypes on the Basis of Genetic Variation: a Systematic Review.Molecular neurobiology · 2024Pooled it
- Integration of Proteomics and Phenomics to Reveal Molecular Differences in High and Low Semen Quality in Donkeys.Reproduction in domestic animals = Zuchthygiene · 2026Article
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- Expression of marker genes to assess the spermatogenic capacity in patients with idiopathic non-obstructive azoospermia.Journal of assisted reproduction and genetics · 2025Article
- hnRNPC Functions with HuR to Regulate Alternative Splicing in an m6A-Dependent Manner and is Essential for Meiosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice.Journal of cell science · 2024Article
- Article
- Gene expression of male pathway genes sox9 and amh during early sex differentiation in a reptile departs from the classical amniote model.BMC genomics · 2023Article
- Genetic variants underlying spermatogenic arrests in men with non-obstructive azoospermia.Cell cycle (Georgetown, Tex.) · 2023Article
- Upregulation of SPINK2 in acute myeloid leukemia.Advances in laboratory medicine · 2023Review
- Transcriptome profiling of the initial segment and proximal caput of mouse epididymis.Frontiers in endocrinology · 2023Article
- Deletion ofCells · 2022Article
- Article
- Omics and Male Infertility: Highlighting the Application of Transcriptomic Data.Life (Basel, Switzerland) · 2022Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- SPINK2 is a prognostic biomarker related to immune infiltration in acute myeloid leukemia.American journal of translational research · 2022Article
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- Elucidating the processes and pathways enriched in buffalo sperm proteome in regulating semen quality.Cell and tissue research · 2021Article
- Towards Post-Meiotic Sperm Production: Genetic Insight into Human Infertility from Mouse Models.International journal of biological sciences · 2021Review
- Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome.JCI insight · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Spermatogenesis is a complex process involving an intrinsic genetic program composed of germ cell-specific and -predominant genes. In this study, we investigated the mouse Spink2 (serine protease inhibitor Kazal-type 2) gene, which belongs to the SPINK family of proteins characterized by the presence of a Kazal-type serine protease inhibitor-pancreatic secretory trypsin inhibitor domain. We showed that recombinant mouse SPINK2 has trypsin-inhibitory activity. Distribution analyses revealed that Spink2 is transcribed strongly in the testis and weakly in the epididymis, but is not detected in other mouse tissues. Expression of Spink2 is specific to germ cells in the testis and is first evident at the pachytene spermatocyte stage. Immunoblot analyses demonstrated that SPINK2 protein is present in male germ cells at all developmental stages, including in testicular spermatogenic cells, testicular sperm, and mature sperm. To elucidate the functional role of SPINK2 in vivo, we generated mutant mice with diminished levels of SPINK2 using a gene trap mutagenesis approach. Mutant male mice exhibit significantly impaired fertility; further phenotypic analyses revealed that testicular integrity is disrupted, resulting in a reduction in sperm number. Moreover, we found that testes from mutant mice exhibit abnormal spermatogenesis and germ cell apoptosis accompanied by elevated serine protease activity. Our studies thus provide the first demonstration that SPINK2 is required for maintaining normal spermatogenesis and potentially regulates serine protease-mediated apoptosis in male germ cells.
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Registered trials
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.