Yamamura K
Institute for Medical Genetics Kumamoto University Medical School.
Gan To Kagaku Ryoho. 1989 Apr;16(4 Pt 1):733-9.
The ability to introduce the cloned gene into the mouse germ line has made possible to analyze the cis-acting DNA sequence which is involved in the tissue-specific and developmental regulation of the gene. In addition, this system can also be applied to analyze the patho-physiological roles of the introduced gene product within the mouse whole body. Therefore, this system is one of the best approaches to analyze the mechanism of oncogenesis. The chromosomal translocation is one of the mechanisms leading to the activation of oncogene. In the case of lymphoid cell tumors, the reciprocal translocation between chromosome No. 8 and No. 14 is frequently observed. With this translocation, c-myc gene can be activated by the enhancer of immunoglobulin heavy chain (E mu). We and others have demonstrated that the E mu-myc gene could induce lymphomas in transgenic mice. Following these observation we have currently many examples that activated oncogene can induce variety tumors, giving basic knowledge about the relationship between activated oncogene and cell-type specificity of tumor. On the other hand, molecular mechanism of oncogenesis which is caused by viruses such as hepatitis B virus (HBV) or human T cell leukemia virus (HTLV) is totally unknown. One main reason is the absence of animal model for these diseases. To overcome this problem, we have attempted and succeeded to produce a transgenic mouse model which consistently produces HBV. Using these mice, it will be possible to elucidate the molecular mechanism of development of hepatitis and hepatocellular carcinoma.
将克隆基因导入小鼠种系的能力使得分析参与基因组织特异性和发育调控的顺式作用DNA序列成为可能。此外,该系统还可用于分析导入基因产物在小鼠全身的病理生理作用。因此,该系统是分析肿瘤发生机制的最佳方法之一。染色体易位是导致癌基因激活的机制之一。在淋巴样细胞肿瘤中,经常观察到8号染色体与14号染色体之间的相互易位。通过这种易位,c-myc基因可被免疫球蛋白重链增强子(Eμ)激活。我们和其他人已经证明,Eμ-myc基因可在转基因小鼠中诱发淋巴瘤。基于这些观察结果,我们目前有许多例子表明激活的癌基因可诱发多种肿瘤,这为激活的癌基因与肿瘤细胞类型特异性之间的关系提供了基础知识。另一方面,由乙型肝炎病毒(HBV)或人类T细胞白血病病毒(HTLV)等病毒引起的肿瘤发生分子机制完全未知。一个主要原因是缺乏这些疾病的动物模型。为了克服这个问题,我们尝试并成功构建了一种能持续产生HBV的转基因小鼠模型。利用这些小鼠,将有可能阐明肝炎和肝细胞癌发生发展的分子机制。