动物造模,药效评价,转基因动物模型 z-bio 2024-07-23 331

　　There are many reports on transgenic animal models of tumor angiogenesis. There are currently three main transgenic mouse models used for tumor angiogenesis:

　　1. The RIP Tag transgenic mouse model is induced by the oncogene SV40Tag and controlled by the insulin gene regulatory region, resulting in pancreatic beta cell tumors. During the embryonic stage of 8-21 days, oncogene expression can be observed, followed by scattered proliferation of islets, of which 50% become highly proliferative islets, exhibiting characteristics of tumor cells in terms of histological morphology and proliferation rate. Among them, 20% have obvious angiogenesis, and 10% can become solid tumors. The histological examination of neovascularization confirms that: ① The precancerous lesions in the RIP Tag transgenic mouse model are very obvious at all stages, with a angiogenesis phase after the proliferative phase. ② New blood vessels grow well before extensive malignant transformation of tumor cells.

　　The BPV1.69 transgenic mouse model is induced by the papillomavirus genome and is a fibrosarcoma of the skin. The tumor formation in this model can be divided into three stages: normal, mild skin fibroadenoma formation, and invasive skin fibroadenoma formation. The three stages are accompanied by the expression of c-jun, jun-B oncogenes, and their related transcription factors AP-1. Von Willebrand (vWF) immunostaining confirmed a significant increase in microvascular density during the formation stage of invasive cutaneous fibroadenoma. The results indicate that vascular activation is initiated before the formation of skin fibrosarcoma. Experiments on in vitro cell lines also showed that during the gradual formation of skin fibrosarcoma, there were corresponding independent vascular initiation stages. The conditioned medium of normal skin cells and mild skin fibroadenoma cells did not promote endothelial cell division and proliferation activity, while the conditioned medium of invasive skin fibroadenoma cells and skin fibrosarcoma cells had endothelial cell division and proliferation activity.

　　The K14-HPV16 transgenic mouse model is derived from basal keratinocytes and mainly expresses the human papillomavirus type 16 oncogene, which is controlled by the keratin 14 gene regulatory region and belongs to epidermal squamous cell carcinoma. This model exhibits activation of angiogenesis initiation at all stages of tumor formation. One month old K14-HPV16 transgenic mice showed a slight increase in capillary density in their dermis, while in the early and advanced stages of their poor proliferation, both the number and distribution density of capillaries were significantly increased. This phenomenon indicates that in this early stage, the formation of low damage blood vessels begins to initiate, transitioning from a quiescent state to moderate degree of neovascularization, while in the highly proliferative and tumor infiltrating stages, there is a significant increase in blood vessel formation.