Knockout Mouse Models
Knockout by gene deletion
A gene Knockout mouse defines an animal model in which, by means of gene targeting, one or more genes of interest are disrupted or inactivated.
The loss of gene activity often causes changes in the phenotype of the model animal, allowing in vivo studies of gene function and biological mechanisms. They are suited as tools for human diseases, pharmacological studies and drug development.
Basically, two approaches are very common:
Constitutive (also called conventional or whole-body) Knockouts
Permanent inactivation of the target gene, and total absence of the protein in the whole animal, in every cell of the organism
Conditional (tissue-specific or inducible) Knockouts
Spatial (in specific tissue or cell types) or temporal (at a given time-point in embryonic, post-natal or adult animals) inactivation of the target gene
Knockout by gene substitution
When studying protein functions or signaling pathways, a gene substitution such as the introduction of a point mutation that causes a loss of function of the protein of interest gives access to a mouse model of higher physiological relevance. Typically, a reporter is introduced at the same time, allowing gene expression monitoring.
Protein function Knockouts
Substitute the gene of interest with a mutation that leads to the loss of protein function
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