动物模型 z-bo 2020-08-04 556

　　[Modeling mechanism] Currently, it is believed that the cause of BCC is mainly related to the abnormal activation of the Shh signaling pathway (sonichedgehog signaling pathway, Shh). This pathway mainly involves Shh, Ptc, Smo and Gli molecules. Both Ptc and Smo are multiple transmembrane proteins, which form a complex in a resting state, and Smo activity is inhibited by Ptc. When Shh binds to Ptc, Ptc no longer inhibits the activity of Smo, Smo can activate the transcription factor Gli and cause a cascade effect in the cell. Abnormal expression of this pathway can lead to the development of BCC. Recent studies have also found that changes in Notch signal are closely related to the occurrence and development of skin tumors. Depending on the transgene or gene knockout technology, the mouse may or may not express a specific gene. You can create basic cell animal models.

　　[Model Features] Transgenic mice overexpressing Shh can spontaneously produce BCC-like changes. Similarly, the precise expression of Shh in time and area is believed to determine the tumor phenotype. Using keratin 1 as a promoter, Shh is overexpressed in hair follicle basal cells. Transgenic mice have a series of abnormal skin changes, such as pigmentation and hair loss, which significantly inhibit the development of follicles.

　　Otch1-/-Because the embryo dies during pregnancy, traditional gene knockout techniques cannot be used to study the function of Notch1 protein. Using tissue-specific gene knockout technology, Notch1 can be specifically knocked out in the epidermis and corneal epithelium of adult mice. In addition, mouse epithelium is highly keratinized and more sensitive to the carcinogenic effects of chemical stimulation. The absence of Notch1 in the skin will cause the expression of Gli2 to continue to increase, eventually leading to BCC-like changes. [Model Evaluation and Application] The cause of BCC is related to factors such as sunlight and excessive arsenic intake, but the exact cause was not known until a transgenic animal model was established. In addition to the etiological search, transgenic animal models are also used to screen clinical treatment drugs. For example, the use of Smo antagonist cyclopamine can significantly reduce the occurrence of BCC in Ptch1 +/- mice induced by uV radiation.