Tyro-3 family receptors are essential regulators of mammalian spermatogenesis

Qingxian Lu, Martin Gore, Qing Zhang, Todd Camenisch, Sharon Boast, Franca Casagranda, Cary Lai, Michael K. Skinner, Rüdiger Klein, Glenn K. Matsushima (), H. Shelton Earp, Stephen P. Goff and Greg Lemke
Additional contact information
Qingxian Lu: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies
Martin Gore: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies
Qing Zhang: Howard Hughes Medical Institute and Department of Biochemsitry
Todd Camenisch: Neuroscience Center and Department of Microbiology
Sharon Boast: Developmental Biology Programme, European Molecular Biology Laboratory
Franca Casagranda: Developmental Biology Programme, European Molecular Biology Laboratory
Cary Lai: Scripps Research Institute
Michael K. Skinner: Center for Reproductive Biology, Washington State University
Rüdiger Klein: Developmental Biology Programme, European Molecular Biology Laboratory
Glenn K. Matsushima: Neuroscience Center and Department of Microbiology
Stephen P. Goff: Lineberger Comprehensive Cancer Center, University of North Carolina
Greg Lemke: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies

Nature, 1999, vol. 398, issue 6729, 723-728

Abstract: 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 Mer1,4. 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 cells5,7. 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.

Date: 1999
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DOI: 10.1038/19554

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