A. CYP2C19 mRNA expression was unexpectedly seen specifically in the brain during embryonic and fetal development in the CYP2C19 transgenic mouse. Brain CYP2C19 mRNA expression peaked at embryonic day 18, with a 6-fold higher expression in brain compared to liver but the expression silenced after birth. Preliminary data indicated that this brain expression of CYP2C19 occurs during fetal development of human brain as well. The morphological brain phenotype at postnatal day 0 in mice homozygous for the genetic insert (CYP2C19) compared to a Wt brain is presented. The CYP2C19 homozygous mice displayed an extensive morphological phenotype with complete callosal agenesis and a less developed and smaller hippocampal formation compared to Wt litter mates, changes indicated by arrows in the images.
B. Adult CYP2C19 transgenic mice displayed an increased anxiety-like behavior as measured by the light-dark box. They spent significantly less time in the light compartment compared to Wt litter mates, thus indicating an anxiogenic-like phenotype.
C. Adult CYP2C19 transgenic mice displayed an increased reactivity to stressful situations as displayed by their behavior in the tail-suspension test and in the open-field. They had an increased total distance travelled in the open-field compared to Wt controls and a significant reduction in immobility time was recorded in adult transgenic mice in the tail-suspension test.
D. Adult CYP2C19 transgenic mice showed a smaller brain and hippocampal volumes as measured by magnetic resonance imaging. Furthermore was the neuron population within the hippocampal formation severely affected with e.g. reduced number of immature neurons. In response to acute stress an increased neuronal activation (increased c-fos expression) was observed in the hippocampus of the transgenic mice thus indicating an altered stress response of the hippocampus in these mice. All data are adapted from [62].
