Epstein-Barr virus (EBV) transgenic animal model
EBV,转基因,动物模型
z-bo
2020-07-25
858
(1) The replication method mainly uses transgene and gene knockout technologies to establish related animal models.
(2) Model functional latent membrane protein (LMP): including LMP-1, 2A, 28. The LMP-1 gene is currently the only confirmed EB virus malignant transformation gene. Animal models related to EBV So far, many animal models related to EBV have not been established, and the focus is mainly on LMP-1 research. Wilson et al. used the immunoglobulin gene promoter Eμ to construct a BNLF-1 (LMP-1 gene) transgene, which is specifically expressed in B lymphocytes. I have a proliferative lesion. Most of them died during development, and there is no experimental evidence that the BNLF-1 gene causes tumors in transgenic animals. The most important reason for failure may be that the correct promoter is not used. Kulwichit et al. used immunoglobulin heavy chain promoters and enhancers to construct LMP-1 gene transgenic mice. B-cell lymphoma is induced in 42% of transgenic mice, and the incidence of B-cell lymphoma increases with age. Only the high expression of LMP-1 in transgenic mice indicates that the LMP-1 oncoprotein plays an important role in the occurrence and development of EBV-related lymphoma. The most important thing to establish an animal model of EBV-related nasopharyngeal carcinoma is to find a tissue-specific promoter. The EBVED-L promoter is a keratinocyte-specific promoter located in the 3'-untranslated region of the LMP-1 gene. Chemical substances such as TPA can increase its activity by 40 times. Akagaw et al. used ED-L2 (a weak promoter present in the EBV genome) to construct a cyclin D1 (Cyclin-D1) transgenic animal. As a result, the oral squamous epithelium, esophagus, and front stomach of transgenic animals grew abnormally, resulting in abnormal cell cycle, epidermal growth factor receptor and p53 protein activity. Using ED-L2 as a relatively specific promoter of squamous epithelium, we have constructed CR2 tissue-specific transgenic mice that are specifically expressed in the mouth and nasopharynx, and there is almost no natural infection with EBV. You can prepare a mouse model. In addition, Huen et al. constructed transgenic mice for EBNA-LP and found that their expression did not affect the incidence of tumors. The toxicity of LP protein can eventually lead to heart failure and death in transgenic animals. Tornell et al. used the SV40 promoter to obtain transgenic animals expressing EBNA-2, and developed renal tubular proliferative lesions in these animals, and subsequently developed renal adenocarcinoma. Wilson et al. used the immunoglobulin gene promoter Eμ to obtain EBNA-1 transgenic mice and the lymphomas that developed in these mice. Recently, Caldwell et al. constructed transgenic mice expressing LMP2A. Studies have shown that LMP2A can provide B cell survival signals that are negative for B cell receptors. Kearns-Jonker and colleagues used immunoglobulin gene promoters to prepare transgenic mice expressing human CR2 and found that less than 5% of peripheral blood B lymphocytes in transgenic mice could be infected by EBV. .. Mouse cells. Ahearn et al. created a knockout animal related to the EBV receptor CR2. The B cell function of mice lacking the Cr2 locus is severely impaired, indicating that CR2/1 is essential for B cell function.
(3) The results of comparative medical serology, epidemiology and molecular biology all show that Epstein-Barr virus is closely related to a variety of human diseases. These diseases are mainly infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s disease, gastric cancer, lymphoproliferative syndrome in immunocompromised hosts, and Epstein-Barr virus-related Hematopoietic syndrome, chronic active sex Prestin-Barr virus. Among infections, T-cell lymphoma, natural killer cell leukemia/lymphoma, empyema-associated B-cell lymphoma, smooth muscle tumors, autoimmune diseases, and nasopharyngeal carcinoma (NPC) are common tumors in China. It is a characteristic tumor. Several provinces in southern China, such as Guangdong, Guangxi, Fujian and Hunan, have the highest incidence of nasopharyngeal cancer in the world. The incidence rate is the highest in the world. With the deepening of research, the role of EBV in the development of nasopharyngeal carcinoma has been paid more and more attention. Research on the genetic structure and function of EB virus has focused on the pathogenesis and etiology of nasopharyngeal carcinoma. The establishment of animal models related to virus entry mechanism has also become a research hotspot. With the advent of more and more new methods and in-depth research on Epstein-Barr virus, it is possible to use this relationship for effective gene therapy of these malignant tumors.
