IL-33 Transgenic Mouse Model for Atopic Dermatitis Research
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current atopic dermatitis model mice generated by genetic engineering do not accurately reflect human atopic dermatitis conditions, as they fail to exhibit key symptoms such as skin-specific IL-33 expression, inflammatory cell accumulation, and IgE levels, making them inadequate for evaluating prophylactic or therapeutic drugs effectively.
Innovation Solution
Creation of transgenic mice with specific skin expression of the IL-33 gene using a keratin promoter, which spontaneously develops dermatitis, increases inflammatory cells, IgE, histamine, and cytokine concentrations, and scratching behavior, mimicking human atopic dermatitis, allowing for the evaluation of drug efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional genetically-engineered atopic dermatitis model mice are used, then drug evaluation can be performed, but the models do not accurately reflect human atopic dermatitis conditions
Solution Approach 1:
The patent changes the expression pattern parameter of IL-33 from constitutive or non-specific expression in conventional models to skin-specific expression driven by the keratin promoter. This parameter change enables the model to accurately reflect human atopic dermatitis where IL-33 is specifically upregulated in skin keratinocytes, thereby improving model reliability while maintaining drug evaluation applicability
2Reliability
If IL-33 is overexpressed in the skin using keratin promoter, then atopic dermatitis symptoms are accurately reproduced, but the complexity of transgenic animal generation increases
Solution Approach 1:
The patent uses the keratin promoter as an intermediary element to achieve skin-specific IL-33 expression. This promoter acts as a regulatory mediator that directs transcription of the IL-33 gene specifically in keratinocytes, enabling accurate phenotype reproduction without requiring complex multi-gene constructs or sophisticated genetic engineering approaches
3Ease of manufacture
If conventional atopic dermatitis models are used, then the models are available for research, but they fail to exhibit key symptoms such as skin-specific IL-33 expression and inflammatory cell accumulation
Solution Approach 1:
The patent applies local quality by restricting IL-33 expression specifically to skin tissue through the keratin promoter, rather than ubiquitous expression. This spatial restriction mirrors the local upregulation of IL-33 in skin keratinocytes observed in human atopic dermatitis, enabling accurate reproduction of localized inflammatory cell accumulation and tissue-specific pathology
Data Source
Figure 1~3
Figure 4
Figure 5~6
AI summary
The present invention provides a transgenic non-human mammal retaining, in a specifically expressible state, a DNA encoding IL-33 in the skin, and having one or more features selected from the group consisting of (1) spontaneous onset of dermatitis, (2) increase in the number of inflammatory cells, (3) increase in total IgE concentration, histamine concentration, cytokine concentration and/or chemokine concentration, and (4) increase in scratching time, under SPF (specific pathogen free) breeding conditions, as compared to a corresponding non-transgenic non-human mammal, and the like.