疾病动物模型,基因修饰淋巴瘤动物模型 z-bio 2021-03-11 348

　　[Modeling mechanism] The occurrence of lymphoma is a multi-factor participation and multi-stage process. A variety of mechanisms such as cell cycle regulation, anti-apoptotic pathways and tumor suppression pathways play an important role in the pathogenesis of lymphoma. Using exogenous methods, combining the molecular level and the overall level, the expression and consequences of a specific gene are reproduced close to reality in the living body. The establishment of a specific transgenic animal model is currently the highest level of experimental system.

　　[Modeling method] In 1985, Adams et al. first constructed a B-cell lymphoma transgenic mouse model in which the myc oncogene was translocated. The myc gene with no regulatory sequence has no biological activity after being transferred, and Ig weight is attached. After chain 5c-end enhancer (Em), it is similar to the translocation of the c-myc proto-oncogene on chromosome 8 and the Ig heavy chain or light chain gene on chromosome 14, chromosome 2, or chromosome 22 in patients with Burkin lymphoma, Each transgenic mouse developed B-cell lymphoma within a few months after birth, further confirming that the high expression of c-myc caused by chromosomal translocation is an important cause of Burkitt lymphoma. Furthermore, t(2;5)(q23;q35) translocation is the most common karyotypic abnormality in anaplastic large cell lymphoma (ALCL), t(2;5) makes the N-terminal domain of NPM/B23 gene and ALK gene forms the fusion gene NPM/ALK, induces the expression of the fusion protein NPM/ALK (or P80), and promotes the occurrence of ALCL. The establishment of the NPM-ALK transgenic mouse animal model provides a solid foundation for elucidating the molecular mechanism of ALK-mediated cell malignant transformation, and further supports the oncogene characteristics of the fusion gene NPM-ALK. There are also gene knock-in models. For example, NSHP-2D61G or SHP-2E76K gene knock-in mice have lymphomas.

　　【Features of the model】Transgenic animal models are also used for lymphoma suppression studies. Multi-gene transgenic animals can be formed by crossing different transgenic animals to study the synergistic effects of different genes in the development of lymphoma. SHP-2D61G or SHP-2E76K mice, after a single irradiation of 400 to 600 rad, most of them developed lymphoma or T cell leukemia.

　　[Model evaluation and application] There are many kinds of transgenic methods, which can be used to replicate animal models. The etiology of lymphoma can be studied at the molecular level, the function and signal transduction pathways of genes related to the occurrence of lymphoma can be studied, and it can also be used to screen antibodies. Cancer drugs have opened up a new way of lymphoma modeling, but there are still certain shortcomings, such as the uncontrollability of gene copy number and the randomness of integration sites. Phenotypic analysis is also difficult, but for now , Transgenic technology is still an effective technology to study tumor occurrence, development, and metastasis. SHP-2D61G mice have typical lymphoma phenotypes such as enlarged thymus and lymph nodes after irradiation.