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Conditional point mutation mouse model-tissue specific

1.Definition

A mouse model where a point mutation is introduced into the target gene in specific cells or tissues. The mutated protein's expression level and profile is accordant with the expression of wildtype gene, and is expressed during the whole mouse development period.

2. Advantages and disadvantages

Advantages: this strategy can avoid a deadly phenotype caused by a conventional point mutation, such as death of the embryonic stem cell, death of the chimeric mouse, or death of the generation F1 heterozygous mouse. The mutated gene is only expressed in specific cells or tissue.

Disadvantages: ensure the mutated gene's expression level and expression profile is accordant with the wildtype gene's expression when designing

3 .Principle

A conditional point mutation is mainly realized with a chromosome locus specific recombinase system, such as the Cre-LoxP system, FLP-Frt system, and the Dre-Rox system, etc., with the most common being the Cre-LoxP system. This system puts the LoxP sequence on the ends of the gene sequence section that will be knocked out, thereby obtaining the Floxed (Flanked by loxP) mouse. Before mating with the mouse expressing the Cre recombinase, the floxed mouse expresses the target gene normally, which can avoid the possible embryonic death caused by whole-gene knockout. The mouse with a target gene knocked out in a specific tissue or cell can be obtained after the floxed mouse mates with the mouse expressing the tissue-specific Cre recombinase, while the gene is expressed normally in other tissues or cells.

If the floxed mouse mates with different mice expressing the Cre recombinase, the target gene knockout can be made in any of the mouse's tissues or cells. The knockout of the target gene can occur in any developmental stage of the mouse if combined with the inducible system controlling the Cre recombinase expression, and the regulation of target gene expression in both time and space can be achieved.

4. Application

Lethal target gene study

Drug target affirmation

Preclinical drug evaluation 


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