Phenotypic characterization of transgenic mice:
choosing the right test battery
B. Bert
Institute of Pharmacology and Toxicology, Free University Berlin, Berlin, Germany
The serotonin (5-HT)1A receptor is associated with a wide range of behavioral and physiological effects, including anxiety-related behavior, 5-HT syndrome, depression, aggression, thermoregulation and food intake. Additionally, learning and memory might also be regulated by this receptor. Knockout studies have confirmed the significance of the 5-HT1A receptor for anxiety-related behavior and depression. To further elucidate the role of this receptor subtype, an inverse approach has been used by generating transgenic mice overexpressing the 5-HT1A receptor.
To study the phenotype of these mice, we chose a test battery that allowed us to assess the main physiological and behavioral paradigms. To evaluate general health, we measured weight gain, body temperature and food intake of homozygous, heterozygous and wildtype mice. Motor functions and exploratory behavior were investigated using the open field and hole board. In addition, home cage activity was controlled. The Morris water maze task was used to assess learning and memory abilities, and the elevated plus maze to investigate emotional behavior.
The homozygous mice differed from the wildtype mice in many of the conducted tests and physiological paradigms. They gained more weight with a simultaneously lower food intake, and showed a lower body temperature. There were no differences in locomomotor activity investigated in a new environment (i.e. the open field and hole board), but in the home cage transgenic mice showed reduced activity. Learning and memory ability were impaired in homozygous mice compared to wildtype mice. Finally, in the elevated plus maze test, homozygous mice demonstrated a decreased level of anxiety-related behavior.
Overall, mice overexpressing the 5-HT1A receptor show behavioral and physiological changes, highlighting the involvement of 5-HT1A receptors in a number of CNS-dependent functions. Furthermore, our data endorse the view that a battery of observational tests and physiological measurements is capable of distinguishing subtle variations in the phenotype of transgenic mice.
This work is supported by DFG grant Fi 491/2-3.
Paper presented at Measuring Behavior 2002 , 4th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands