Psychiatric disorder-related abnormal behavior and habenulointerpeduncular pathway defects in Wnt1-cre and Wnt1-GAL4 double transgenic mice

The neural crest is a unique structure in vertebrates. Wnt1-cre and Wnt1-GAL4 double transgenic (dTg) mice have been used in a variety of studies concerning neural crest cell lineages in which the Cre/loxP or GAL4/UAS system was applied. Here, we show psychiatric disorder-related behavioral abnormalities and histologic alterations in a neural crest-derived brain region in dTg mice. The dTg mice exhibited increased locomotor activity, decreased social interaction, and impaired short-term spatial memory and nesting behavior. The choline acetyltransferase-and vesicular glutamate transporter 2-immunoreactive habenulointerpeduncular fiber tracts that project from the medial habenular nucleus of the epithalamus to the interpeduncular nucleus of the midbrain tegmentum appeared irregular in the dTg mice. Both the medial habenula nucleus and the interpeduncular nucleus were confirmed to be derived from the neural crest. The findings of this study suggest that neural crest-derived cells have pathogenic roles in the development of psychiatric disorders and that the dTg mouse could be a useful animal model for studying the pathophysiology of mental illness such as autism and schizophrenia. Scientists that use the dTg mice as a cre-transgenic deleter line should be cautious in its possible toxicity, especially if behavioral analyses are to be performed.