ATF6α controls the levels of ER chaperones and ERAD component in the dopaminergic neuron system under physiological conditions in vivo. A, ATF6α controls the mRNA levels of BiP in the brainstem, the midbrain and the striatum in mice brain in vivo. Total RNA was isolated from various sections of brain of 3 and 12-month-aged male ATF6α KO(−/−) mice and ATF6α WT(+/+) littermates and analyzed by quantitative real-time RT-PCR for detecting the level of BiP mRNA. (n = 5 for each group). Fold induction of mRNA level is defined relative to GAPDH mRNA level. Abbreviation: CTX, cerebral cortex; BS, brainstem; HIP, hippocampus; STR, striatum; MB, midbrain; CR, cerebellum; OB, olfactory bulb; T, thalamus; SC, spinal cord; 3 m, 3 months aged group; 12 m, 12-month-aged group. The asterisk indicates statistical significance (*, p < 0.05; **, p < 0.01). Each bar denotes the mean ± S.D. B, ATF6α controls the protein levels of BiP in the brainstem, the midbrain and the striatum in mice brain in vivo. The tissue lysates of 3-month-aged ATF6α KO mice and ATF6α WT littermate were subjected to Western blot analysis for detection of BiP and β-actin (n = 5). Each protein level was quantified using optical density and estimated relative to β-actin protein level. C, ATF6α controls the levels of GRP94, p58IPK, and Derlin-3 in the midbrain in vivo. Quantitative real-time RT-PCR was performed from the midbrain samples of 12-month-aged ATF6α KO mice and ATF6α WT littermates using ATF6α, GRP94, p58IPK, and Derlin-3 primers (n = 5 for each group). D, ATF6α controls the protein levels of BiP and GRP94 in the striatum in vivo. (n = 7–10). E, metabolisms of dopamine and serotonin were decreased in ATF6α KO mice as compared with ATF6α WT mice. Metabolisms of dopamine and serotonin were defined as the relative ratio of DOPAC or HVA to dopamine and 5HIAA to 5HA, respectively. The striatal levels of dopamine, serotonin, and their metabolites were measured by HPLC (n = 8–10 for each group). Abbreviations: DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; HVA, homovanillic acid; 5HIAA, 5-hydroxyindole acetic acid; 5HA, 5-hydroxytryptamine; 6 m, 6-month-aged group; 12 m, 12-month-aged group.