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胚胎发育中的潜在作用 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 此外，c-mos在生长的卵母细胞中转录， mos RNA在萌发囊泡期积累。卵母细胞c-mos RNA在转录后与卵母细胞一起被多聚腺苷酸化 成熟，并通过中期至晚期两个细胞阶段降解，这表明 c-MOS作为母体信息的可能作用。因为c-mos代表 是卵母细胞特有的调节性母体RNA的第一个候选者， 进一步研究其在精子发生中的表达。合成、 c-mos蛋白的磷酸化和稳定性将在 精母细胞、卵母细胞、卵和胚胎。c的生物学功能 卵母细胞中的mos将通过抑制c-mos表达来研究， 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改变相关， 鉴定c-MOS蛋白激酶活性候选靶点。监管 序列和反式作用因子控制c-mos表达， 将研究精母细胞和卵母细胞的成熟， c-mos在精子发生中表达的发育特异性， 进一步研究。额外选择的原癌基因的表达 将在精子发生、卵子发生和植入前小鼠中进行研究 胚胎这些关于正常原癌基因在发育过程中功能的研究 也将有助于理解癌基因 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.