Figure 3. Clock∆19 results in ER stress in mice. (A) TEM depicting the luminal diameter of the ER in WT and Clock∆19 hepatocytes. Clock∆19 mouse hepatocytes show the expansion of the ER (blue arrow; n=4 for all groups). (B) Relative expression assessed by qPCR of the UPR pathway genes in the liver of WT and ClockΔ19 mice from 16 weeks of age. Note that the expression of Grp94, Grp78, Chop and Perk were significantly increased in Clock∆19 mice. Data were normalized to Gapdh expression (n=4). **, P < 0.01 and *, P < 0.05. (C-D) Immunoblots of liver tissue from WT and Clock∆19 mice at ZT0 and ZT12; the UPR proteins GRP94, GRP78, (p)PERK and (p)eIF2α are significantly activated in Clock∆19 mice. β-ACTIN is a loading control. **, P < 0.01 and *, P < 0.05 versus control. n=4 mice per group.