Doctoral defence: Jane Varul „Different stress coping strategies of 129Sv and C57/Bl6 mouse strains - evidence from behavioural, pharmacological, metabolomics and gene expression studies“

On 12 January at 15:00 Jane Varul will defend her doctoral thesis "Different stress coping strategies of 129Sv and C57/Bl6 mouse strains - evidence from behavioural, pharmacological, metabolomics and gene expression studies". 

Supervisors:
Professor Eero Vasar, University of Tartu
Associate Professor Mari-Anne Philips, University of Tartu
research fellow Jürgen Innos, niversity of Tartu

Opponent: 
Dr Silvia Mandillo, National Research Council (Italy) 

Summary
The most widely used animal model in preclinical studies is the laboratory mouse (Mus musculus domesticus) because they are similar to humans, both genetically and biologically. The most common mouse strains in biomedical applications are C57/Bl6 (Bl6) and 129Sv. The dissertation provides an overview of the differences between the two strains - 129Sv and Bl6 - which would allow researchers to better choose the line required to solve a specific research task.

The study showed higher behavioral activity of Bl6 line. Thereafter, the effect of amphetamine on locomotor activity was evaluated. Amphetamine treatment is applied in preclinical settings to investigate the basic mechanisms of psychotic conditions. Bl6 mice receiving acute (one time injection of) amphetamine displayed significantly higher motor activity compared to 129Sv mice. However, repeated administration of amphetamine elevated activity more in the 129Sv line, but not in all animals, as in half of the mice the activity remained the same as in acute administration group. A similar effect is present in human population where methamphetamine causes in some individuals addiction, but others develop psychosis.

The metabolomic studies revealed that in adaptation to the environment, Bl6 mice use glucosis-related pathways whereas the 129Sv line tends to favor lipid metabolism.

Based on the behavioural response of mice to amphetamine and the gene expression studies, it was concluded that the activity of the dopaminergic system in the brain of Bl6 mice is higher than that of 129Sv mice. Furthermore, studies of protein expression suggested that EGF, ERBB1 and GRIN1 in the frontal cortex may be the biomarkers related with better environmental adaptation.

In conclusion, the Bl6 mouse line seems to be more suitable for elucidating the mechanisms of drug dependence, and 129Sv mice offer better opportunities to investigate depression and psychosis-like conditions.