Crnn Knockout Mice for Psoriasis Modeling
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Solution Overview
Problem
Current animal models for studying skin inflammation disorders like psoriasis do not adequately replicate the human condition, limiting understanding and treatment development.
Innovation Solution
Genetically modified rodents with a loss of function mutation in the Crnn gene, specifically Crnn knock-out mice, are developed to serve as a more susceptible model for skin inflammation, incorporating a reporter gene for enhanced monitoring and induced psoriasis-like conditions using imiquimod treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current animal models are used for studying skin inflammation disorders, then the research can proceed with existing models, but the models do not adequately replicate the human condition, limiting understanding and treatment development
Solution Approach 1:
The patent modifies the genetic parameters of the rodent model by introducing a loss-of-function mutation in the Crnn gene, which encodes cornulin, a protein involved in epidermal differentiation. This genetic parameter change results in a rodent model that more accurately replicates human psoriasis pathology, including epidermal hyperplasia, parakeratosis, and inflammatory infiltrates, thereby improving the reliability of the model for studying skin inflammation disorders
2Reliability
If a loss of function mutation is introduced in the Crnn gene to create a more susceptible model, then the susceptibility to skin inflammation increases, but the genetic modification complexity increases
Solution Approach 1:
The patent applies the extraction principle by specifically targeting and disrupting the Crnn gene through a loss-of-function mutation. This involves removing or inactivating the specific gene responsible for cornulin production, thereby creating the desired susceptibility to skin inflammation while maintaining the rest of the genome intact. This focused genetic modification approach reduces overall complexity compared to more comprehensive genomic alterations
3Measurement precision
If reporter gene is incorporated for enhanced monitoring, then the monitoring capability is improved, but the device complexity increases
Solution Approach 1:
The patent merges the reporter gene (such as LacZ, GFP, or luciferase) with the Crnn gene locus to create a fusion construct. This merging allows the reporter gene to be expressed under the control of the Crnn promoter and enhancer elements, enabling monitoring of Crnn expression patterns and skin inflammation responses. The combined construct achieves enhanced monitoring capability while leveraging the natural regulatory elements of the Crnn gene to minimize the need for additional complex regulatory components
Data Source
Figure 1
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Figure 2E~2G
AI summary
This disclosure relates to a genetically modified rodent and use thereof as a rodent model. More specifically, this disclosure relates to rodent (e.g., mouse or rat) comprising a loss of function mutation in an endogenous Crnn (cornulin) gene, and to use of such a rodent animal as a rodent model of skin inflammation disorders (e.g., psoriasis).