| OCR Text |
Show 115 (Calhoon and Tye, 2015). Most studies have focused on the middle two steps, interpretation and evaluation, with very complex circuity network mainly in the amygdala, the bed nucleus of the stria terminalis, the ventral hippocampus and the PFC, activation of which ultimately trigger the HPA axis in the response initiation step (Calhoon and Tye, 2015). Our Lef1 animal models likely have defects in this last response initiation step of the anxiety circuity, where its key effector CRH is connected to Crhbp in zebrafish and Drosophila, and possibly Pmch in mice (section 4.2.7). Notably, sex difference is prevalent in stress responses (Bale and Epperson, 2015). In our study, both male and female mouse mutants displayed reduced body weight gain, which we believe is secondary to an anxiety phenotype (Chapter 3). However, the body growth defect is less severe in females than males: the reported statistical significance was drawn from over 25 animals per sex per genotype; if the standard 10-12 animals were used, a statistical difference would only be observed in males, but not in female mutants (not shown). This interesting observation appears to be consistent with the anxiety test result. Male mutants have elevated anxiety in both open field test (OFT) and elevated plus maze (EPM) test, whereas such phenotype was only shown in female mutants in estrus using OFT. It is not clear why the anxiety phenotype in the female mutants was not detected in the EPM. One possible confounding factor could be anxiety conditioning from the OFT, which was not eliminated yet in the EPM performed one day after the OFT. The estrous cycle-dependent anxiety phenotype in the female OFT is interesting, possibly leading to a less severe body growth phenotype in females which were not controlled for estrous cycle during weight measurement. However, there is a possibility that checking estrous cycle may stress the animals to a degree that impacts the following anxiety tests (Gangitano et |
