疾病动物模型,基因修饰特应性皮炎动物模型 z-bio 2021-03-15 319

　　Genetically modified mice are very valuable tools in determining the physiological functions of specific genes and proteins and their roles in disease states. Different genetically modified mice show the characteristics of diseases from their own perspectives, which are useful for studying the pathogenesis of diseases. And the development of drugs provides broad prospects and helps clarify the role of individual cytokines and proteins in the occurrence and pathogenesis of AD, as well as biological therapy.

　　【Modeling mechanism】The mechanism of atopic dermatitis transgenic or gene knockout animal model is similar to that of other genetically modified disease animal models.

　　[Model features] K14-IL-4-Tg/CbyB6 mice overexpress IL-4 under the regulation of the keratin 14 promoter. At the age of 4 months, the mice spontaneously develop chronic pruritic skin lesions, and the early skin pathology manifests as horns. Excessive transformation, mild hypertrophy of the spinous layer, degranulation of mast cells and mononuclear cell infiltration. Late stage manifested as hypokeratosis and eosinophil infiltration. Serum total IgE and IgG1 levels increased. The mouse also has the performance of impaired skin barrier function, which is easy to cause staphylococcal pyoderma.

　　"The IL-18 gene expressed by keratinocytes was transferred into C57BL/6 mice to breed KIL-18Tg mice. At 6 months of age, the mice developed AD-like skin lesions. The skin pathology showed thick spinous layer, degranulation of mast cells, and infiltration of lymphocytes and neutrophils.

　　"Other transgenic animal models include IL-1β converting enzyme (CASP1) transgenic mice, IL-31 transgenic mice, thymic stromal lymphopoietin (TSLP) transgenic mice, and APOCl transgenic mice. All models can spontaneously develop AD-like skin lesions at the appropriate age, and the cellular immunity is mainly Th2.

　　The NC/Ng mouse model of knocking out STAT6 gene (STAT6-/- Nc mouse) is also an important model for AD research. Although this mouse cannot express IgE and Th2 cytokines, it can produce AD-like dermatitis, and the skin lesions have a significant expression of half Caspase 1, IL-18, IL-12 and IFN-γ. Other gene knockout animal models include IL-4, IFN-γ, IL-5, IL-10 gene-deficient mice, cathepsin E (Cat E) knock-out mice, and RelB gene-deficient mice.

　　[Model evaluation and application] Like other genetically modified animal models, AD transgenic or gene knockout animal models provide a platform for in vivo research on the functions of key factors, revealing the important role of specific factors in the occurrence and development of AD. These models also It can be a tool for studying cytokines or factor receptor antagonists to facilitate clinical drug screening.