Cre-LoxP Autoantigen Model for Stable Antibody Production
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Solution Overview
Problem
Current animal models for autoimmune diseases, such as Graves' disease, require repeated antigen administration and suffer from immune tolerance and leaky expression issues, making them ineffective for reproducing autoimmune disease symptoms and mechanisms.
Innovation Solution
A gene delivery system using the Cre-LoxP system to introduce autoantigen genes into animals, allowing for controlled expression of autoantigens via Cre recombinase treatment, enabling the production of autoantibodies necessary for disease reproduction without immune tolerance or leaky expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If repeated antigen administration is used to induce autoimmune disease in animal models, then autoimmune symptoms can be reproduced, but the process requires extensive time and repeated treatments over weeks
Solution Approach 1:
The autoantigen gene is pre-introduced into the animal's genome through the Cre-LoxP system, establishing the genetic basis for autoantigen expression before disease induction is needed. This preliminary genetic modification eliminates the need for repeated antigen administrations, as the animal will continuously produce the autoantigen endogenously, thereby reproducing autoimmune symptoms without time-consuming repeated treatments
2Reliability
If conventional gene delivery methods are used to introduce autoantigen, then autoantigen expression can be achieved, but immune tolerance and leaky expression occur reducing model effectiveness
Solution Approach 1:
The Cre-LoxP system acts as an intermediary mechanism between the introduced autoantigen gene and its expression. The loxP sites serve as specific recognition sequences that mediate precise genetic recombination when Cre recombinase is introduced, enabling controlled activation of the autoantigen gene while avoiding immune tolerance and leaky expression that occur with conventional delivery methods
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for the efficient and stable induction of autoimmune diseases in animal models, effectively reproducing symptoms and mechanisms with a single treatment, overcoming the limitations of existing models.
Implementation Method 1
introduction of autoantigen gene into the animal through Cre-LoxP system enables the expression of the autoantigen at a desired time point only by treating Cre recombinase
Data Source
AI summary
The present invention relates to an autoimmune disease animal model and a method for preparing the same. The animal model of the present invention efficiently generates an autoantibody that causes autoimmune disease, by introducing an autoantigen-encoding gene through the Cre-LoxP system, which enables stable and continuous expression of the autoantigen at a desired time by treatment of Cre recombinase. Contrary to the conventional method that fails to effectively produce autoantibody due to leaky expression and immune tolerance, or requires repeated administration over several weeks, the present invention achieves sustainable expression of an effective amount of autoantigen by only one TAT-Cre recombinase treatment, thus may be utilized as an outstanding animal model reproducing various symptoms and molecular mechanisms of autoimmune diseases.