Testicular tumor susceptibility at the agouti locus

抑制睾丸生殖细胞肿瘤(TGCT)进展的基因特征 将提高我们对原始生殖细胞(PGC)发育的理解，并为 治疗人类TGCT的新靶点。缺失Raly和Raly的/4y突变 Eif2s2并导致agti的异位表达，降低129/Sv对TGCT的敏感性 和129只Chr19M小鼠。相比之下，初步研究表明，&gt；Avy突变 维持Raly和Eif2s2并从IAP插入诱导agti的异位表达， 不降低129只Chr19M小鼠的TGCT频率。综合起来，这些结果表明 Raly或Eif2s2的缺失，而不是agei的普遍表达，会降低TGCT 在Ay小鼠中的频率。Raly和Eif2s2在RNA生物学中都有不同的功能，其中 在PGC发展和TGCT进展中发挥核心作用。因此，Raly和Eif2s2是 优秀的候选TGCT抑制基因。这项提议将考验1) Raly和Eif2s2缺失对129小鼠TGCT频率降低的影响 BAG转基因互补试验和条件性基因敲除小鼠，2)TGCT Raly和Eif2s2在129./W和129.Chr19M，Avy/小鼠中的频率和表达水平。

Characterization of genes that suppress testicular germ cell tumor (TGCT) progression in mice will improve our understanding of primordial germ cell (PGC) development and provide new targets for the treatment of TGCTs in humans. The /4y mutation, which deletes Raly and Eif2s2 and causes the ectopic expression of agouti, decreases TGCT susceptibility in 129/Sv and 129.Chr19M mice. In contrast, preliminary studies suggest that the >Avy mutation, which maintains Raly and Eif2s2 and induces the ectopic expression of agouti from an IAP insertion, does not decrease TGCT frequency in 129.Chr19M mice. Together these results suggest that the deletion of Raly or Eif2s2 and not the ubiquitous expression of agouti decreases TGCT frequency in Ay mice. Both Raly and Eif2s2 have distinct functions in RNA biology, which plays a central role in PGC development and TGCT progression. Therefore, Raly and Eif2s2 are excellent candidate TGCT suppressor genes. This proposal will test 1) the contributions of the Raly and Eif2s2 deletions on the decreased TGCT frequency in 129.Chr19M, Ay/+ mice using BAG transgene complementation tests and conditional knockout mice, and 2) the TGCT frequency and expression levels of Raly and Eif2s2 in 129./W+ and 129.Chr19M, Avy/+ mice.