动物模型 z-bo 2020-08-04 607

　　Transgenic mice are valuable tools to determine the physiological functions of specific genes or proteins and their role in pathology. From a unique point of view that helps to study the cause of the disease, various transgenic mice exhibit disease characteristics. In addition, drug development provides broad prospects, helping to reveal the pathogenesis and etiology of AD, as well as the role of individual cytokines and proteins in biological therapy.

　　[Modeling mechanism] The mechanism of transgenic or gene knockout animal models of atopic dermatitis is similar to that of other transgenic animal models. [Model features] K14-IL-4-Tg/CbyB6 mice overexpress IL-4 under the control of the keratin 14 promoter, and chronic pruritic skin lesions spontaneously appear in the early skin of 4-month-old mice The lesion is hyperkeratosis, mild hypertrophy of the spinous process layer, degranulation of mast cells and infiltration of monocytes. Late stage manifested as hyperkeratosis and eosinophil infiltration. Serum total IgE and IgG1 levels increased. The skin barrier function of mice is also impaired, which can easily cause staphylococcal pyoderma. The IL-18 gene expressed by keratinocytes was transferred to C57BL/6 mice to breed KIL-18Tg mice. The mice developed AD-like skin lesions at 6 months of age. The skin pathology showed a thick spinous process, 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 interstitial liposome (TSLP) transgenic mice and APOC1 transgenic mice. All models can spontaneously develop into AD-like skin damage at the appropriate age, and Th2 dominates cellular immunity.

　　The NC/Ng mouse model of STAT6 gene (STAT6-/-Nc mouse) is also an important model for AD research. The mouse cannot express IgE and Th2 cytokines, but expresses caspase-1, IL-18, IL-12, IFN-γ, which can cause AD-like dermatitis and severe skin lesions. Other gene knockout animal models include IL-4, IFN-γ, IL-5, IL-10 gene-deficient mice, cathepsin E (CatE) gene knockout mice and RelB gene-deficient mice.

　　[Model Evaluation and Application] Like other transgenic animal models, AD transgenic or gene knockout animal models provide a platform for studying the function of key factors in the body and the development of AD. And reveal the important role of certain factors in the pathogenesis. The model can also be used as a tool to study cytokine or factor receptor antagonists and promote clinical drug screening.