疾病动物模型,基因修饰基底细胞癌模型 z-bio 2022-01-12 285

　　[Modeling mechanism] It is currently believed that the cause of BCC is mainly related to the abnormal activation of the Shh signaling pathway (Sonic hedgehog signaling pathway, Shh). This pathway mainly involves molecules such as Shh, Ptc, Smo and Gli. Both Ptc and Smo are transmembrane proteins, they form a complex when they are at rest, and Smo activity is inhibited by Ptc. When Shh binds to Ptc, Ptc no longer inhibits the activity of Smo, and Smo can activate the transcription factor Gli, thereby causing intracellular cascade effects. Abnormal expression of this pathway can lead to the development of BCC. Recent studies have shown that changes in Notch signal are also 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 animal models of basic cells.

　　[Model Features] Transgenic mice overexpressing Shh may spontaneously undergo BCC-like changes. It is also believed that the accurate expression of Shh in time and area determines the tumor phenotype. When keratin 1 is used as a promoter, Shh is overexpressed in the basal layer of hair follicles. Transgenic mice have a series of abnormal skin changes, including: obvious inhibition of pigmentation, hair loss and embryonic hair follicle development. otch1-/-Traditional gene knockout techniques cannot be used to study the function of the Notch1 protein, because the embryo will die during pregnancy. Using tissue-specific gene knockout technology, Notch1 can be specifically knocked out in the epidermis and corneal epithelium of adult mice. Facts have proved that mouse epithelial cells are hyperkeratinized and are more sensitive to the carcinogenic effects of chemical stimulation. In the absence of Notch1 on the skin, Gli2 expression increases, continues to be expressed, and eventually leads 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 clarified until a transgenic animal model was established. In addition to studying the cause, transgenic animal models are also used to screen clinical therapies. For example, the use of the Smo antagonist cyclopamine can significantly reduce the incidence of BCC in UV-induced Ptch1 +/- mice.