the other hand, the findings in this study may also suggest that maintaining FoxO1 transcriptional activity in brain is necessary to stabilize mood and prevent depression developed under environmental changes, such as stress. A limitation of this study was that the brain FoxO1 knockout mice were generated originally from a mouse line containing floxed alleles of FoxO1, 3a, and 4. During selection for behavior tests, no homozygous FoxO3a knockout mouse was included in the tests. Since FoxO4 expression was limited in brain (62, 63), no FoxO4 genotype was excluded during selection, and there was no significant behavioral difference noticed between Nestin-Cre:FoxO4-floxed and wild type mice (data not shown). To avoid this potential limitation, we tested FoxO3a behavior phenotypes in another line of mice that were only lack of FoxO3a.
