• Why knockout mice are important
• No progress
• A phone call
• Aggressive French mice
• Getting the mice to Los Angeles
• Testing the mice: They’re MAO A knockout mice
• A Gift from heaven
Why experiment with mice?
One of the best ways of determining the different functions of MAO A and MAO B is using experiments with knockout mice, where it is possible to study how these enzymes behave in a living system (in vivo).
Animals are useful models for scientists to study the biological basis of behavior and disease. There is a high degree of similarity between animal and human genes. Experimental conditions are more easily controlled in animals than in humans.
Dr. Shih decided to use mice because they are the least expensive animal that can be used for transgenic studies (when a foreign gene – a transgene – is incorporated into the genome of an organism). Fish are another alternative to mice, but mice are closer to the human genetic makeup than fish.
How do you ‘knock out’ the MAO A or B gene?
Dr Shih explains how knockout mice are made in her lab. A colony of knockout mice were bred from these mice.
Normally, one uses homologous recombination, a method of replacing a portion of DNA with a modified gene construct to create a MAO-deficient mouse.
Creating MAO-deficient mice
• How it began
• Breeding mice for MAO deficiency
• How it is done
• Founder mice
MAO A mice and aggression
What happens when MAO A is ‘knocked out’?
In this video Dr. Shih describe MAO A deficiency and explains why MAO A-deficient mice fight and other behaviors that can be studied.
Role of serotonin in anxiety and aggression
This video describes MAO, the use of mice and the possibilities of gene therapy
• MAO A-deficient mice
• Drug development and blocking the serotonin receptor
• Gene therapy
• Where we are now?
MAO A knockout mice before and after drug treatment
Hyper-reactive MAO double knockout mice
Hyperreactivity in mice: knockout mice vs normal mice.
Voice over: Dr. Kevin Chen
A double knockout mouse and its wild-type sibling
Dr. Kevin Chen describes the different behavior based on the following:
• Double KO mice versus wild-type mice
• Siblings and identifying mutants
• How double KO mice were discovered
• A new environment
Two ways of treating aggressive behavior in mice
Fears
In his pioneering study of a Dutch family with several generations of violent males, clinical geneticist Dr. Han Brunner has provided the first tangible evidence of a direct link between molecular biology (a MAO A deficiency) and aggressive behavior in humans.
Fears
• Muller-Hill’s objections
• The threats posed by these discoveries
• We all have to think about this
The aggression gene?
In his pioneering study of a Dutch family with several generations of violent males, clinical geneticist Dr. Han Brunner has provided the first tangible evidence of a direct link between molecular biology (a MAO A deficiency) and aggressive behavior in humans.
The aggression gene?
• Why this isn’t the aggression gene
• Extremely rare
• Non-specific phenotype
• It’s not written in the gene
• Modifiable
MAO AB Deficient Boy
MAO AB Deficient Infant
Mouse Models of MAO B Knockout and MAO AB Knockout
