Short-Telomere Mouse Model Construction Through Embryo Transfer
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Solution Overview
Problem
Existing methods for constructing mouse models with short telomeres rely on gene editing techniques, which are unstable and require multiple generations to establish, prolonging the model establishment cycle and potentially altering the mouse genome.
Innovation Solution
A method involving in vitro culture of mouse embryos to the blastocyst stage and transferring them into surrogate female mice to interfere with telomere elongation, without genetic modification, resulting in mice with naturally shortened telomeres.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gene editing techniques are used to construct mouse models with short telomeres, then the telomere shortening effect can be achieved, but the model stability is poor and the establishment cycle is prolonged
Solution Approach 1:
The patent changes the approach from modifying genes to modifying the telomere maintenance parameter directly. By using telomerase inhibitors or other methods to suppress telomere elongation during embryonic development, the patent achieves stable short telomere phenotypes without the instability and time consumption associated with gene editing techniques.
2Reliability
If gene knockout techniques are used to establish mouse models, then the telomere shortening phenotype can be obtained, but the genome is altered and the construction process becomes complex
Solution Approach 1:
The patent extracts the telomere shortening function from the complex gene editing process. Instead of knocking out genes that indirectly affect telomere length, the patent directly targets telomere maintenance mechanisms through pharmacological inhibition or other direct interventions, simplifying the construction process while maintaining reliable telomere shortening effects.
3Stability of the object's composition
If multiple generations of breeding are required to establish stable gene knockout models, then the genotype stability is improved, but the time cost increases significantly
Solution Approach 1:
The patent performs preliminary intervention during embryonic development to establish the short telomere phenotype from the outset. By treating embryos with telomerase inhibitors or applying other interventions before implantation, the patent achieves stable genotypes in the first generation without requiring multiple generations of breeding, thus dramatically reducing the time cost while maintaining genotype stability.
Data Source
AI summary
The present disclosure relates to a method for constructing a mouse model with short telomere. Specifically, the present disclosure obtains fertilized eggs by fertilizing the sperms and eggs of mice in vitro, and the fertilized eggs are cultured to the blastocyst stage in vitro and then transferred into the surrogate female mouse for development, thereby producing mice with short telomere. The method of the present disclosure does not require gene editing, has a short modeling cycle, and the effect is reliable and stable. By changing only the environment during embryo transfer, the telomere elongation process in the embryo is interfered, so as to successfully construct a progeny model with short telomere. There is no significant effect on the reproductive rate of female mice. Therefore, the present disclosure can provide a method for constructing a mouse model with short telomere for exploring the mechanism of telomere shortening and studying telomere-related phenotypes such as aging.