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
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature. 1999 Apr 22;398(6729):723-8. doi: 10.1038/19554.
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.
我们已经在小鼠基因中产生并分析了编码三种具有酪氨酸激酶活性的结构相关受体（Tyro 3、Axl和Mer）的无效突变。缺乏任何一种单一受体或两种受体的任何组合的小鼠都能存活且可育，但缺乏所有三种受体的雄性动物由于分化中的生殖细胞逐渐死亡而无法产生成熟精子。这种退化表型似乎是由于生精小管的支持细胞通常提供的营养支持失败所致，其功能取决于睾酮和睾丸间质细胞产生的其他因子。Tyro 3、Axl和Mer在出生后发育过程中均由支持细胞正常表达，而它们的配体Gas6和蛋白S在性成熟前由睾丸间质细胞产生，之后由睾丸间质细胞和支持细胞共同产生。在这里，我们表明支持细胞中Tyro 3、Axl和Mer的协同激活对于这些细胞作为发育中生殖细胞的滋养细胞所起的作用至关重要。其他观察结果表明，这些受体对于成熟神经、免疫和生殖系统中多种细胞类型的营养维持也可能至关重要。
