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 vivostudies 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

‍