JAK3 Knockout Mini-Pig SCID Model Construction
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Solution Overview
Problem
Current severe combined immunodeficiency (SCID) animal models, particularly those with JAK3 gene mutations, do not accurately replicate human immune system characteristics, limiting their effectiveness in research and treatment applications.
Innovation Solution
A recombinant expression vector and transgenic cell line are developed using the CRISPR/Cas9 system to knock out the JAK3 gene in mini-pigs, creating a SCID animal model with a specific deficiency in the JAK3 gene, mirroring human SCID phenotypes and enabling more accurate research and potential treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If JAK3 knock-out mice are used as SCID animal models, then the immune system phenotype is established, but the model shows significant differences from human immune system characteristics
Solution Approach 1:
The patent creates a mini-pig SCID model by copying the JAK3 knock-out approach from mice to pigs, which have immune systems more similar to humans. This allows the SCID phenotype to be replicated while improving the model's representativeness of human immune system characteristics.
Solution Approach 2:
The patent changes the species parameter from mouse to mini-pig while maintaining the JAK3 knock-out condition. This parameter change enables the model to exhibit both SCID phenotype and human-like immune system characteristics simultaneously.
2Productivity
If conventional SCID animal models are used, then research can be conducted, but the models do not accurately replicate human immune system characteristics
Solution Approach 1:
The patent copies the successful JAK3 knock-out model from mice to mini-pigs, creating a new model that maintains research productivity while improving the accuracy of human immune system characterization through species selection.
Solution Approach 2:
The patent changes the species parameter from mouse to mini-pig to improve the measurement precision of human immune system characteristics while preserving the SCID phenotype necessary for research.
3Reliability
If JAK3 knock-out mice are used, then T cell development interference is observed, but thymic hypoplasia is more severe compared to IL2rg knock-out mice
Solution Approach 1:
The patent copies the JAK3 knock-out model to mini-pigs, allowing observation of T cell development interference without the extreme thymic hypoplasia seen in mice, as pigs naturally have more robust thymus development.
Solution Approach 2:
The patent changes the species parameter to mini-pig, which modifies the severity of thymic hypoplasia while maintaining the T cell development interference phenotype, thereby providing a more balanced model for research.
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
The JAK3 knock-out mini-pig model exhibits a phenotype similar to human SCID, lacking thymus, lymphocytes, and Peyer's patches, making it suitable for research, artificial blood development, and xenotransplantation, while providing a more accurate representation of human immune system dysfunction.
Implementation Method 1
this research team used the genetic scissors (CRISPR/Cas9) system to delete the JAK3 gene in mini-pig somatic cells
Data Source
AI summary
The present disclosure relates to a JAK3 gene-mutated severe combined immunodeficiency animal model and a method of constructing the same. In the JAK3 gene-mutated severe combined immunodeficiency animal model of the present disclosure, the JAK3 gene is specifically deficient, the expression of cytokines is regulated by controlling the number and activity of macrophages, and the thymus, lymphocytes, and Peyer's patches, which are observed in conventional severe combined immunodeficiency animal models, particularly mini-pigs, are completely lacking. In addition, the animal model of the present disclosure can be used as a treatment model for JAK3 SCID patients, as similar phenotypes are observed in patients with human severe combined immunodeficiency caused by a JAK3 gene mutation, and can be used for artificial blood development or xenotransplantation.