动物造模,自发性银屑病 z-bio 2023-10-09 903

　　There are three common types: squamous skin mutant mice, spontaneous chronic proliferative dermatitis mutant mice, and sebum deficient mutant mice.

　　1. Scaly skin mutant mice were hybridized from A/J inbred strain mice and BALB/c mice, and this strain of mice can spontaneously develop psoriasis like dermatitis. At birth, all mice were normal except for hypochromic anemia. As mice age, they gradually develop excessively keratinized plaques, hypertrophic spinous layers, and elongated skin processes. Mice can also exhibit changes such as hair pits, stripes, and nail curvature, as well as scaly thickening of the nail bed. After tearing the skin with adhesive tape, Kobner phenomenon can occur. These phenotypes can be reversed after oral administration of cyclosporine A, topical application of epidermal growth factor, or exposure to medium wave ultraviolet (UVB) radiation. In addition, homozygous mice with this mutation are often accompanied by gastric hyperplasia. The shortcomings of this model lie in the lack of obvious T cell infiltration in histopathology, and the need for mice to live in a sterile environment to prevent dermatophyte infection.

　　2. Spontaneous Chronic Proliferative Dermatitis Mutant Mouse Model: This mutant mouse was first found in a group of C57BL/KalwRij mice in the Netherlands. Due to the invisible mutation of chromosome 15, the normally normal mice began to develop erythema, thinning of hair, and obvious scales on the back and ventral sides (starting at the nape) at 2-3 weeks of age. Interestingly, the skin lesion gradually extends to the entire skin, except for the ears, foot pads, and tail. Mice usually develop severe skin ulcers due to unbearable itching, and are euthanized at 20-30 weeks. Histology shows that mice initially exhibit focal epidermal proliferation, which expands to diffuse at or after the 5th week. The main characteristics of this disease are excessive orthokeratosis, spinous layer hypertrophy, and patchy dyskeratosis. Scattered apoptotic keratinocytes can be seen in the Malpighian basal layer, which exhibit isolated, atrophic, and bright eosinophilic granules, and are positive for TUNEL detection. The epidermis is often accompanied by infiltration of eosinophils and the formation of pustules within the stratum corneum. Dermal infiltration is mainly composed of eosinophils and a small amount of mast cells, macrophages, and neutrophils. Skin ulcers caused by scratching can reach deep into the muscular layer and eventually heal through granulation, pseudoepithelial tumor like hyperplasia, re epithelialization, and dermal fibrosis.

　　3. Spontaneous mutations in the stearoyl CoA dehydrogenase 1 gene in BALB/cCrglGa mice, a mouse model of hyposebum mutation, can lead to a phenotype of hyposebaceous hairlessness. Homozygotes can be confirmed on the 7th day due to delayed epidermal growth, worsening hair loss, and becoming almost hairless by adulthood. Skin cell proliferation is quite obvious at birth and gradually worsens with age. Fibroblasts with abnormal morphology, collagen and elastin remodeling can be seen in the dermis. The hair follicles begin to function normally, but quickly become abnormal. The inner hair root sheath cells block the hair tubes and hinder the growth of new hair. The sebaceous glands exist, but have abnormal differentiation and rarely secrete sebum. Homozygotes exhibit depilation, underdeveloped sebaceous glands, eye wetting disorders, triglyceride synthesis and storage disorders, scaly skin, and growth retardation.