Overview
While traditional knockout models are powerful tools for gene function analysis, they have a critical limitation: permanent gene deletion in all cells where the gene is active. Conditional knockout (cKO) models solve this problem by controlling when and where a gene is inactivated using site-specific recombinases.
How Conditional Knockouts Work
The most widely used system is Cre-lox recombination. A floxed allele is created with LoxP sites flanking an essential exon. When crossed with Cre-expressing mice, the gene is deleted only in tissues where Cre is active.
Advantages
Conditional knockouts avoid embryonic lethality, enable tissue-specific studies, allow temporal control of gene deletion, reduce confounding systemic effects, and better model diseases with tissue-restricted pathologies.
Frequently Asked Questions
What's the difference between a conditional and a constitutive knockout?
A constitutive knockout removes a gene in every cell throughout the organism's life. A conditional knockout removes the gene only in specific tissues or at specific developmental stages.
How is a conditional knockout triggered?
Conditional knockout is triggered by Cre recombinase expressed under a tissue-specific or inducible promoter, which excises the floxed exon in target cells.
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