动物造模,药效评价,淋巴瘤 z-bio 2024-09-04 483

　　The occurrence of lymphoma is a multifactorial and multi-stage process. Various mechanisms such as cell cycle regulation, abnormal anti apoptotic pathways, and tumor suppressor pathways play important roles in the pathogenesis of lymphoma. The use of exogenous methods to combine molecular and global levels, to reproduce the expression and consequences of a specific gene in vivo, and to establish a specific transgenic animal model, is currently the highest level of experimental system.

　　In 1985, Adams et al. first constructed a transgenic mouse model of B-cell lymphoma with a translocation of the myc oncogene. The myc gene, which was removed from the regulatory sequence, had no biological activity after being transferred. After adding the Ig heavy chain 5c enhancer (Em), similar to the translocation of the original oncogene on chromosome 8 and the Ig heavy or light chain genes on chromosomes 14, 2, or 22 in Burkin lymphoma patients, each transgenic mouse developed B-cell lymphoma within a few months after birth, further confirming that chromosomal translocation leading to high expression of myc is an important cause of Burkitt lymphoma. Furthermore, t (2; 5) (q23; q35) translocation is the most common karyotype abnormality in anaplastic large cell lymphoma (ALCL), t (2; 5) Forming a fusion gene NPM/ALK by fusing the N-terminal domain of NPM/B23 gene with ALK gene, inducing the expression of fusion protein NPM/ALK (or P80), and promoting 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 cellular malignant transformation, and further supports the oncogene characteristics of the fusion gene NPM-ALK. There is also a gene knock in model. Both NSHP-2D61G and SHP-2E76K gene knockout mice developed lymphoma.

　　[Model Features] Transgenic animal models are also used for lymphoma suppression research. Multi gene transgenic animals can be formed through hybridization between different transgenic animals to study the synergistic effects of different genes in the occurrence and development of lymphoma. SHP-2D61G or SHP-2E76K mice mostly develop lymphoma or T-cell leukemia after a single irradiation of 400-600rad.

　　There are currently many methods of genetic modification for replicating animal models, which can be used to study the etiology of lymphoma at the molecular level, the function and signal transduction pathways of lymphoma related genes, and the screening of anticancer drugs. This has opened up a new path for modeling lymphoma, but there are still certain shortcomings, such as the uncontrollability of gene copy numbers and the randomness of integration sites. Phenotypic analysis also poses certain difficulties. However, currently, genetic modification technology is still an effective technique for studying tumor occurrence, development, and metastasis. SHP-2D61G mice exhibit typical lymphoma phenotypes such as thymus enlargement and lymph nodes after irradiation.