Assessing Social Dominance in Mouse Models Using the Tube Test

The goal of my research is to find new therapies for frontotemporal dementia caused by progranulin mutations. We found that the tube test correlates with social dominance deficits, and is a good outcome measure for preclinical screening of potential therapeutics. The tube test is simple to perform and analyze.

It can be used repeatedly on the same mice for longitudinal testing of age or treatment effects. Finally, we know the neural circuits that drive tube test behavior, which helps interpret results. So we use the tube test as the primary outcome measure in our preclinical studies.

Try to end up find new therapeutic strategies for former of frontal frontotemporal dementia due to progranulin mutations. Our results support the use of two different therapies, anti-transthyretin antibodies and progranulin gene therapy, both of which have now progressed in the human clinical trials for this disorder. To begin, obtain the PVC tubing with a length of 30.5 centimeters.

Place all cages containing mice of the same sex to be tested on a cart. Transport the cages to the testing area. Place the two cages for the first match on the testing surface.

Remove the lids and place them beside each cage. Locate the two mice to be tested. Hold one mouse in each hand corresponding to its assigned side of the tube.

After identifying the first mouse, gently hold its tail and keep it in the cage while searching for the second mouse. Simultaneously, remove both mice from each cage and gently place them with their heads at the entrance to the tube. Maintain a grip on each mouse's tail to prevent premature contact.

Once both mice have entered the tube, release the tails and step away from the tube. Observe the match and record the winner and loser. A mouse is considered to have lost the match when two of its paws, exit the tube and contact the testing surface.

After the match is over, return the mice to their home cages. Clean the tube and the testing surface with 70%ethanol. Begin each round immediately after the preceding round.

Once all matches for one sex are completed, return the cages to the rack or cart. After testing is complete, clean both the tubes and testing area with 2%chlorhexidine Progranulin heterozygous mice exhibited lower social dominance compared to progranulin wild type mice at nine to 16 months of age with the low dominance phenotype being stable over repeated testing. Both male and female heterozygous mice exhibited lower social dominance in within cage dominance hierarchy tests, whereas progranulin knockout mice did not display this abnormality.

The heterozygous mice injected with a control adeno-associated virus continued to show low social dominance, while the ones injected with a progranulin boosting adeno-associated virus no longer exhibited the low social dominance phenotype.