Sequence of LTR of mouse mammary tumor virus and its regulatory factors

在本项目中，得出了以下结论。1)克隆了内源性小鼠乳腺肿瘤病毒（MMTV）在乳腺肿瘤高发的SHN小鼠株中的长末端重复序列（long terminal repeat， LTR），并对其序列进行了解析。在280 ~ 380个密码子的开放阅读框中，与已报道的小鼠MMTV序列相比，发现了许多碱基变化。相比之下，目前LTR的调控区序列得到了很好的保存。2)在皮肤中发现MMTV DNA以染色体外DNA片段的形式存在，证明其是一个完整的MMTV基因组。然而，它在MMTV复制过程中的作用仍然未知。3)已知能量限制（ER）抑制MMTV基因表达，但其机制尚不清楚。我们发现内质网诱导的麻木，反过来又抑制了各种器官的细胞增殖。然而，由于能源消耗或住房温度的增加，抑制作用有所缓解。4)我们发现内质网特异性地降低了RNA的总量和细胞的数量。而PRL mRNA被ER降低的程度远大于actin mRNA，表明PRL mRNA比其他基因的降低更为深刻。5) ER后微粒体Aa^<++>- atp酶活性降低。在恒温体温下，它们在大脑、肝脏和唾液腺中的活性降低，在异温体温下，它们在这些腺体和肾脏中的活性降低。

In the present project, the following findings were made.1) The long terminal repeat (LTR) of endogenous mouse mammary tumor virus (MMTV) in the SHN mouse strain, known to have a high incidence of mammary tumors, was cloned and its sequence was elucidated. In the open reading frame between 280 and 380 codons, many base changes were found when compared with reported murine MMTV sequences. In contrast, the sequence of regulatory area of the present LTR was well preserved.2) The MMTV DNA was found to exist as extrachromosomal DNA fragments in the skin and was proven that it is an entire whole MMTV genome. Its role in the MMTV replicating processes, however, remains unknown.3) It has been known that energy restriction (ER) suppresses gene expression of MMTV, although its mechanisms still remains unknown. We found that ER induced torpor and it, in turn, suppressed cellular proliferation in various organs. Suppression, however, was alleviated by increases in energy consumption or in housing temperatures.4) We found that ER decreased the total amount of RNA specifically as well as numbers of cells. PRL mRNA was, however, decreased by ER to much greater extent than that in actin mRNA, suggesting that PRL mRNA decreased more profoundly than other genes.5) Activities of microsomal Aa^<++>-ATPase was found to be decreased after ER.Their activities were found to be decreased at euthermic body temperatures in brain, liver, and salivary glands, and in these and kidney at heterothermic body temperatures.