Humanized IL-15 Mouse Model for Accurate Immune Cell Development
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Solution Overview
Problem
Existing rodent models for human immune system research are limited by species specificity, making it difficult to directly extrapolate findings to humans, and there is a need for a more accurate animal model for studying humanized immune cell development and drug screening.
Innovation Solution
Development of a mouse model with a humanized IL-15 gene comprising specific exons of both human and mouse IL-15 genes, utilizing a CRISPR/Cas9 system for genetic modification, allowing for the creation of a mouse model with a reconstituted humanized immune system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If rodent models are used for human immune system research, then experimental feasibility is improved, but species specificity causes conclusions to be difficult to extrapolate to humans
Solution Approach 1:
The patent applies local quality by replacing only the IL-15 gene coding region with the human ortholog while retaining the mouse gene structure and regulatory elements. This localized humanization of the specific gene of interest allows researchers to study human IL-15 function in a rodent system, improving extrapolation accuracy for IL-15-mediated immune responses while maintaining the experimental feasibility of using mouse models.
2Reliability
If a fully humanized immune system model is created, then relevance to human immunity is improved, but model complexity and difficulty of construction increase
Solution Approach 1:
The patent extracts and replaces only the specific IL-15 gene coding region with the human ortholog, rather than attempting to create a fully humanized immune system. This selective approach focuses resources on the critical gene of interest, improving human relevance for IL-15 studies while avoiding the prohibitive complexity of comprehensive immune system humanization.
Solution Approach 2:
The patent implements partial humanization by replacing only the essential coding exons (exons 2-4) of the IL-15 gene, which is sufficient to produce human IL-15 protein with correct amino acid sequence. This partial action achieves the necessary human relevance without the excessive complexity of complete immune system humanization.
Data Source
AI summary
Provided are a mouse and a functional activity part thereof, comprising a humanized IL-15 gene; the humanized IL-15 gene comprises a human IL-15 gene segment and a mouse IL-15 gene segment, the human IL-15 gene segment comprises at least a part of exon 4, exon 5, exon 6, exon 7 and exon 8 of the human IL-15 gene, and the mouse IL-15 gene segment comprises exon 1, exon 2 and exon 3 of the mouse IL-15 gene. Also provided are a preparation method and use of the mouse.