Animal Models

Question 1

What is the difference between constitutive and conditional knockouts?

Answer 1

• Conventional KO is where the gene is knocked out in the whole animal
• Conditional KO is where you can control where and when the gene is knocked out

Question 2

How can conditional knockout be done?

Answer 2

Cre-Lox system:

• Utilises a signle enzyme, called Cre recombinase
• This enzyme recombines two Lox sequences
• Hence, if the two Lox sequences are placed around a gene of interest, the Cre recombinase will cut the gene out
• To make the KO conditional, the Cre recombinase is driven under a promoter that has restricted expression (e.g. insulin-driven Cre is used to look at beta cell function)
• To make the KO inducible, the Cre recombinase can be complexed with a ligand-binding domain of the estrogen receptor -> The Cre recombinase cannot get into the nucleus unless there is tamoxifen present

Question 3

Summarise the main types of KO mice.

Answer 3