Figure 2. The reduction in peripheral WBC counts in hepatocytes is positively correlated with the bioenergetic deficit in the liver.

(A) Coa5^hep (n = 6; P < 0.001) and (B) Cox10^hep (n = 15–16; P < 0.01) mice also exhibit a significant leukopenia. (C) Coa5^hep mice (purple bars) have a disproportionate reduction in the wet weight of the spleen (n = 6; P < 0.01) and thymus (n = 5; P < 0.001), while Cox10^hep mice (blue bars) exhibit significant yet milder atrophy of the spleen (n = 14; P < 0.05). Significance was assessed using a 2-tailed Student’s t test (A–C). (D) Total WBC counts are positively correlated with liver ATP content in all 3 hep mouse models (linear regression R² = 0.99; P = 0.001). P47 Sco1^hep and P64 Cox10^hep livers have higher levels of (E) the phosphorylated form of eIF2α, an ISR marker, and (F) the Atf6 transcript, a marker of ER stress (1-way ANOVA with Tukey’s post hoc test, n = 4–6; P < 0.005, Sco1^hep model; P < 0.02, Cox10^hep model).