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Method for building human psoriasis mouse model and application of model

A mouse model, psoriasis technology, applied in animal husbandry and other directions, to achieve the effect of convenient use and simple construction method

Inactive Publication Date: 2015-02-11
应哲康
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these mice have obvious non-specific gene knockout, which brings a very unfavorable factor to these mice as animal models of psoriasis

Method used

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  • Method for building human psoriasis mouse model and application of model
  • Method for building human psoriasis mouse model and application of model
  • Method for building human psoriasis mouse model and application of model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Embodiment 1SM22-CreIKK2 Flox / Flox mouse build

[0049] 1. Experimental materials

[0050] SM22-Cre transgenic mice were purchased from Jackson Laboratory (strain number 004746); the Cre enzyme expression sequence of this strain of mice is under the control of the tissue-specific promoter SM22.

[0051] IKK2 Flox / Flox Mice, purchased from the Michael Karin laboratory, are genetically engineered mice; this strain of mice has a Cre enzyme recognition sequence inserted into the IKK2 gene. When Cre enzyme exists, the IKK2 gene part of the cell will be knocked out, thereby Completely inactivate the IKK2 gene.

[0052] 2. Experimental method and analysis

[0053] 1) Construction of experimental mice:

[0054] via SM22-CreIKK2 Flox / Flox with IKK2 Flox / Flox paired to produce experimental mice, such as figure 1 As shown, through two generations of hybridization, we obtained SM22-CreIKK2 Flox / Flox mice, and at the same time obtain littermate IKK2 as a control Flox / Flox ...

Embodiment 2I

[0067] Phenotype analysis of the human psoriasis mouse model of embodiment 2IKKA gene selective knockout

[0068] 1. Observation of mouse phenotype

[0069] At three weeks of age, IKK2 in the same litter Flox / Flox Control mice and SM22-CreIKK2 Flox / Flox After mice were anesthetized, photographic analysis was performed.

[0070] The result is as Figure 6 As shown, the hollow arrow points to the psoriasis-like lesions, and the solid arrow points to the ulcer-like lesions. SM22-CreIKK2 Flox / Flox The mice developed two distinct lesions: on the head and tail, the mice with lesions on the head had lesions that were very similar to human psoriasis; on the buttocks, they showed ulcer-type lesions. It can be seen that the human psoriasis mouse model (SM22-CreIKK2) of the IKK2 gene selective knockout of the present invention Flox / Flox ) can indeed show psoriasis-like lesions in specific parts of mice, including the head and tail.

[0071] 2. Immunofluorescence Analysis

[0072]...

Embodiment 3

[0084] Genetic Analysis of Embodiment 3 Human Psoriasis Mouse Model

[0085] 1. Experimental method

[0086] The SM22-CreIKK2 three weeks after birth constructed in Example 1 Flox / Flox Mice with IKK2 Flox / Flox Mice were crossed, and the genotype distribution of the first generation of hybrids was shown in Table 2; the relationship between the time of lesion occurrence and the growth cycle of mice was shown in Table 3; the model mice of the first generation of hybrids were analyzed by photography at 20 weeks , Figure 10 It is representative of various psoriasis-like lesions.

[0087] Table 2 The genotype distribution of the first generation of offspring

[0088]

[0089] Table 3 Relationship between focus and growth cycle of mice

[0090]

[0091]

[0092] 2. Analysis of experimental results

[0093] According to the distribution of genotype and sex of offspring in Table 2, SM22-CreIKK2 Flox / Flox There is no significant difference between the development of gen...

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Abstract

The invention relates to the technical field of animal models and in particular relates to a method for building a human psoriasis mouse model and application of the model to drug screening. The method adopts a conditional gene targeting technology and comprises the following steps: creating a marked mouse with homologous loxP sites on the two sides of an IKK2 gene through a homologous recombination process, hybridizing the marked mouse with a mouse with Cre recombinase expression under the control of a tissue-specific promoter SM22, and screening to obtain the human psoriasis mouse model. The human psoriasis mouse model has the advantages that the building method is simple, convenient and economic, and the psoriasis expression of the human psoriasis mouse model is highly similar to that of a human body; moreover, the animal model is convenient to use and has market values and medical application prospects.

Description

technical field [0001] The invention relates to the technical field of animal models, in particular to a method for constructing a mouse model of human psoriasis and its application in drug screening. Background technique [0002] Psoriasis is the most common skin disease in humans. The typical cutaneous appearance is well-demarcated erythematous plaques with silvery white scales. In mild cases, it may manifest as several silver coin-sized plaques on the elbow and knees, and in severe cases, the skin of the whole body may also be involved. Difficult to cure and easy to relapse is an important clinical feature of the disease. The etiology of psoriasis is complex. So far, the specific etiology of the disease has not been determined, and studies have shown that the occurrence of the disease is mainly related to the combined effects of genetic factors, infection, metabolic disorders, immune dysfunction, and endocrine disorders. [0003] The histopathological features of the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/02
CPCA01K67/0275A01K2217/206A01K2227/105A01K2267/0325
Inventor 应哲康陈敏婕
Owner 应哲康
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