Transgenic Mouse Expressing Human Coxsackie Virus Receptor
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Solution Overview
Problem
There is a lack of a suitable animal model for viral diabetes inducibility that satisfies Koch's postulates, specifically due to the absence of human coxsackie group B virus receptor expression in mouse pancreatic islet cells.
Innovation Solution
A transgenic mouse is created that expresses the human coxsackie group B virus receptor (hCXADR) specifically in pancreatic beta cells, making these cells susceptible to infection with human coxsackie group B viruses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional transgenic animal models express virus receptors in non-pancreatic cells or use non-mouse species, then virus-induced diabetes can be observed, but the model does not accurately reflect human viral diabetes pathogenesis
Solution Approach 1:
The patent applies local quality by expressing the human coxsackie virus receptor specifically in pancreatic beta cells rather than systemically throughout the organism. This localized expression in the target tissue (pancreatic islet cells) creates a more accurate model of human viral diabetes pathogenesis, where the virus specifically infects beta cells to cause insulin deficiency and diabetes.
Solution Approach 2:
The patent uses copying by introducing the human receptor gene (CXADR) into mouse pancreatic beta cells, creating a transgenic model that copies the human receptor system into the mouse. This allows human coxsackie B virus to infect mouse beta cells in a manner that replicates human disease mechanisms, enabling valid study of viral diabetes pathogenesis in a mouse model.
2Adaptability or versatility
If human coxsackie virus receptor is introduced into mouse pancreatic beta cells, then the mouse becomes susceptible to human coxsackie B virus infection, but this requires complex transgenic manipulation
Solution Approach 1:
The patent uses an intermediary approach by employing a viral vector or transgenic manipulation system to deliver and integrate the human CXADR gene into mouse pancreatic beta cells. This intermediary mechanism enables the transfer of the human receptor system into the mouse model, creating virus susceptibility without requiring complex breeding programs or multiple genetic modifications.
3Ease of manufacture
If existing transgenic models use non-specific receptor expression or different virus receptors, then transgenic mice can be produced, but they cannot develop diabetes upon coxsackie B virus infection
Solution Approach 1:
The patent resolves this contradiction by implementing local quality through pancreas-specific or beta cell-specific expression of the human CXADR receptor. This targeted expression ensures that only pancreatic beta cells express the human receptor, making them susceptible to coxsackie B virus infection and subsequent diabetes development, while maintaining feasibility of transgenic production through specific promoter-driven expression.
Solution Approach 2:
The patent applies parameter changes by modifying the expression pattern of the receptor gene - changing from non-specific or systemic expression to pancreas-specific expression. This parameter change in spatial expression pattern enables both successful transgenic production and reliable diabetes development upon virus infection, as the receptor is precisely where needed in the pancreas.
Data Source
AI summary
Provided is a transgenic mouse that expresses a human coxsackie group B virus receptor gene specifically in pancreatic beta cells. The transgenic mouse has DNA encoding a human coxsackie group B virus receptor in pancreatic beta cells and expresses the human coxsackie group B virus receptor specifically in the pancreatic beta cells.