动物造模 z-bo 2022-05-19 410

　　[Modeling mechanism] The development of lymphoma is a multi-factor, multi-step process. Various mechanisms such as cell cycle regulation, anti-apoptotic pathways and tumor suppression pathways play an important role in the pathogenesis of lymphoma. By using exogenous methods to combine the molecular level and the overall level, the expression and results of specific genes can be replicated in the body in a more realistic way. At present, the establishment of specific transgenic animal models is the highest level of experimental system.

　　[Modeling method] In 1985, Adams et al. constructed the first B-cell lymphoma transgenic mouse model in which the myc oncogene was transferred. After the Ig heavy chain 5 c-terminal enhancer (Em), it is similar to the c-myc proto-oncogene on chromosome 8 and the Ig heavy chain or light chain gene on chromosome 14, 2 or 22 in patients with Birkin lymphoma. I'm. Every transgenic mouse develops B-cell lymphoma in the first few months of life, further confirming that the high expression of c-myc caused by chromosomal translocation is an important cause of Burkitt lymphoma. In addition, t(2; 5) (q23; q35) translocation is the most common karyotypic abnormality in anaplastic large cell lymphoma (ALCL), and t(2; 5) is the N-terminal domain of the NPM/B23 gene. The ALK gene forms the fusion gene NPM/ALK, which induces the expression of the fusion protein NPM/ALK (or P80) and promotes the development of ALCL. The establishment of the PM-ALK transgenic mouse animal model provides a solid foundation for elucidating the molecular mechanism of ALK-mediated malignant transformation of cells, and further supports the carcinogenicity of the fusion gene NPM-ALK. I will. There is also a gene knock-in model. For example, NSHP-2D61G or SHP-2E76K knock-in mice have lymphoma. [Characteristics of the model] Transgenic animal models are also used to study lymphoma suppression, and multi-gene transgenic animals are formed by mating different transgenic animals to study the synergistic effect of different genes in the development of lymphoma. were able. Most SHP-2D61G or SHP-2E76K mice will develop lymphoma or T-cell leukemia after receiving 400-600ad radiation.

　　[Model Evaluation and Application] There are a variety of transgenic methods that can be used to replicate animal models, and it is possible to study the etiology of lymphoma at the molecular level, and to study the function and signal transduction of genes related to the occurrence of lymphoma. You can research the route. Screening anti-cancer drugs has opened up new methods for lymphoma modeling, but it also has certain defects, such as uncontrolled gene copy numbers and random integration sites, making phenotypic analysis difficult. In other words, transgenic technology is an effective technology for studying tumor occurrence, development and metastasis. SHP-2D61G mice have a typical lymphoma phenotype, including enlarged thymus and lymph nodes after irradiation.