PROTO-ONCOGENES IN GAMETOGENESIS AND EARLY DEVELOPMENT

拟议研究的总体目标是调查 原癌基因在哺乳动物配子发生和早期发育中的潜在作用 胚胎发育。C-mos、c-abi和int-1原癌基因是 在小鼠精子发生的特定阶段转录。在……里面 此外，c-mos在发育中的卵母细胞中转录，高水平的c-mos MOS-RNA在生发泡期积累。卵母细胞c-mos 核糖核酸在转录后与卵母细胞结合形成多聚腺苷 成熟，并在两个细胞的中后期退化，这表明 C-mos作为母性信息的可能作用。因为c-mos代表 第一个候选的是卵母细胞特有的调节性母体RNA， 进一步研究其在精子发生中的表达。综合， C-mos蛋白的磷酸化和稳定性将在#年研究。 精母细胞、卵母细胞、卵子和胚胎。C-蛋白的生物学功能 将通过抑制c-mos的表达来研究卵母细胞中的mos 反义寡核苷酸和/或抗MOS抗体。这些研究 将与蛋白质磷酸化的变化相关 确定c-mos蛋白激酶活性的候选靶点。监管 调控c-mos基因表达的序列和反式作用因子 将研究精母细胞和卵母细胞的成熟度，并 C-mos表达在精子发生中的发育特异性将是 进一步研究。其他选择性原癌基因的表达 将在精子发生、卵子发生和植入前小鼠中进行研究 胚胎。关于发育过程中正常原癌基因功能的研究 也将有助于理解致癌基因 诱导肿瘤转化。

The overall goal of the proposed research is investigation of the potential roles of proto-oncogenes in mammalian gametogenesis and early embryonic development. The c-mos c-abi and int-1 proto-oncogenes are transcribed during specific stages of spermatogenesis in the mouse. In addition, c-mos is transcribed in growing oocytes and high levels of c- mos RNA are accumulated by the germinal vesicle stage. The oocyte c-mos RNA is post-transcriptionally polyadenylated in concert with oocyte maturation and is degraded by the mid to late two cell stage, suggesting possible roles for c-mos as a maternal message. Since c-mos represents the first candidate for a regulatory maternal RNA unique to oocytes, further studies with its expression in spermatogenesis. Synthesis, phosphorylation and stability of the c-mos protein will be studied in spermatocytes, oocytes, eggs and embryos. The biological functions of c- mos in oocytes will be investigated by inhibiting c-mos expression using anti-sense oligonucleotides and/or anti-mos antibodies. These studies will be correlated with alterations in protein phosphorylation to identify candidate targets for c-mos protein kinase activity. Regulatory sequences and trans-acting factors which control c-mos expression during maturation of spermatocytes and oocytes will be investigated and the developmental specificity of c-mos expression in spermatogenesis will be further studied. The expression of additional selected proto-oncogenes will be studied in spermatogenesis, oogenesis and pre-implantation mouse embryos. These studies of normal proto-oncogene function in development will also contribute to understanding the mechanisms by which oncogenes induce neoplastic transformation.