Because of the tissue- and cell type-specific expression of ERK5; the selectivity, specificity, and sustainability of Nestin-CreERTM-driven erk5 deletion; and a demonstrated role for ERK5 in adult neurogenesis, the ERK5 icKO mice provide an excellent animal model to examine a functional role of adult hippocampal neurogenesis in the etiology of anxiety and depression, since other brain regions outside of the adult neurogenic zones are not affected in the ERK5 icKO mice. This evidence concerns the gene NES and major depressive disorder.