Transgenic Mice Expressing Human Siglec Proteins
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current animal models are unsuitable for studying human Siglec protein functions due to high evolutionary divergence, making it challenging to develop effective models for in vivo studies of Siglec proteins and their roles in human diseases such as Alzheimer's disease and cancer.
Innovation Solution
Transgenic non-human animals, such as mice, are developed to express multiple human Siglec genes like CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, and Siglec-14, which recapitulate the expression patterns of these proteins in human cells, allowing for the investigation of their functional and pathological properties and the testing of therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current animal models are used to study human Siglec protein functions, then research can be conducted in vivo, but the models are unsuitable due to high evolutionary divergence between mouse and human Siglec proteins
Solution Approach 1:
The patent creates transgenic mice that express human Siglec proteins instead of mouse Siglec proteins. This copying approach allows the animal model to display the exact human protein sequences of interest (CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16), thereby resolving the evolutionary divergence problem while maintaining the in vivo research capability
Solution Approach 2:
The transgenic mouse model combines mouse biological systems with human Siglec protein expression. This composite approach integrates the advantages of in vivo animal modeling with the specific human protein sequences, creating a hybrid system that overcomes the limitation of pure mouse models
2Reliability
If transgenic animals expressing multiple human Siglec genes are developed, then suitable models for studying human Siglec functions and diseases are obtained, but the complexity of generating and maintaining such models increases
Solution Approach 1:
The patent develops transgenic mice that can express multiple different human Siglec proteins (CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16) within the same animal model system. This multi-functional approach allows a single transgenic line to serve multiple research purposes across different Siglec family members, reducing the need for separate models for each protein
Data Source
AI summary
Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire.