Tyro-3 family receptors are essential regulators of mammalian spermatogenesis
Abstract
We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer. Mice lacking any single receptor, or any combination of two receptors, are viable and fertile, but male animals that lack all three receptors produce no mature sperm, owing to the progressive death of differentiating germ cells. This degenerative phenotype appears to result from a failure of the tropic support that is normally provided by Sertoli cells of the seminiferous tubules, whose function depends on testosterone and additional factors produced by Leydig cells. Tyro 3, Axl and Mer are all normally expressed by Sertoli cells during postnatal development, whereas their ligands, Gas6 and protein S, are produced by Leydig cells before sexual maturity, and by both Leydig and Sertoli cells thereafter. Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells. Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems.
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Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice.
“Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice”
From Hypoxic control of metastasis (2016) · cites this paper as [87]
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- Authors
- Lu, Q., Gore, M., Zhang, Q., Camenisch, T., Boast, S., Casagranda, F., Lai, C., Skinner, M. K., Klein, R., Matsushima, G. K., Earp, H. S., Goff, S. P., & Lemke, G.
- Affiliations
- Salk Institute for Biological Studies (US)
- Howard Hughes Medical Institute (US)
- European Molecular Biology Laboratory (DE)
- Scripps Research Institute (US)
- Washington State University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Matsushima, Glenn K.
- ORCID
- Venue
- Nature
- Published
- 1999-04
- Volume
- 398
- Issue
- 6729
- Pages
- 723-728
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1646925026
- Cited by
- 514
- References
- 31
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 24 · 2023: 23 · 2022: 23 · 2021: 28 · 2020: 22 · 2019: 34 · 2018: 26 · 2017: 21 · 2016: 23 · 2015: 18 · 2014: 32 · 2013: 23 · 2012: 12
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- AXL, Mer, receptor tyrosine kinase, spermatogenesis, germ cell death, Sertoli cells, Leydig cells, Gas6, protein S, seminiferous tubules, male infertility, null mutations, receptor ligands
- MeSH terms
- c-Mer Tyrosine Kinase, Axl Receptor Tyrosine Kinase, Growth Arrest-Specific Protein 6, Animals, Leydig Cells, Ligands, Male, Mice, Mutant Strains, Phenotype, Proteins, Proto-Oncogene Proteins, Sertoli Cells, Spermatogenesis, Oncogene Proteins, Gene Expression, Protein S, Neural Cell Adhesion Molecules, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Mice
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