Conditional knockout of Deaf1 in neuronal precursors produces anxiety behavior in adult mice

Abstract

DEAF1 is a DNA binding protein and the first transcription factor to be linked to suicide and depression. In humans with major depressive disorder (MDD), DEAF1 is reported to have altered expression in the prefrontal cortex and the dorsal raphe nucleus of females but not males, and may therefore function in sex‐specific depression. To better understand the role of DEAF1 in the regulation of behavior, we have produced a mouse line with conditional gene targeting (Deaf1‐flox). Deaf1‐flox mice were bred to congenic status onto a C57BL/6 background, and were then bred to mice transgenic for the nestin‐Cre gene to produce embryonic knockout of Deaf1 in neuronal precursor cells. Adult mice were tested for anxiety behavior using the Elevated Plus Maze and Open Field Exploration tests. Relative to control mice, both male and female mice with homozygous deletion of Deaf1 in brain displayed decreased exploration of open spaces while staying preferentially near enclosed spaces, as measured by the amount of time spent and distance traveled in those spaces. Our results indicate that conditional knockout of Deaf1 in neuronal precursors produces anxiety behavior in adult mice, and that this new mouse model may be useful in understanding the molecular mechanisms resulting in MDD. This work was supported by National Institutes of Health Grants CA89438, CA137556, and HD060122.