Genetic disruption of circadian organization promotes alcohol-induced intestinal hyperpermeability.

<p>(<b>A</b>) Urinary sucralose excretion was measured as an index of colon permeability. Alcohol-fed <i>Clock^Δ19/Δ19</i> mutant mice (CA, n = 8–14/week) exhibited increased intestinal permeability compared to alcohol-fed wild-type mice (WTA, n = 8–11/week), control-fed <i>Clock^Δ19/Δ19</i> mutants (CD, n = 8–10/week) and control-fed wild-type mice (WTD, n = 8–9/week). Overall, significant effects of diet (p<0.01) and genotype (p<0.01) were observed. *p<0.05, three-way ANOVA followed by <i>post-hoc</i> Tukey-Kramer Multiple-Comparison test. (<b>B</b>) Average daily diet intake (normalized to body weight) over the duration of the experiment. Alcohol-fed <i>Clock^Δ19/Δ19</i> mutant mice (CA) did not consume more alcohol than wild-type littermates (WTA). *p<0.05, two-way ANOVA followed by <i>post-hoc</i> Tukey-Kramer Multiple-Comparison test. (<b>C</b>) Serum collected at ZT6 was assessed for alcohol levels using gas chromatography. Alcohol-fed <i>Clock^Δ19/Δ19</i> mutant mice (CA) exhibited significantly increased serum alcohol compared to alcohol-fed wild-type mice (WTA) and control diet-fed <i>Clock^Δ19/Δ19</i> mutants (CD). *p<0.05, **p<0.01; two-way ANOVA followed by <i>post-hoc</i> Tukey-Kramer Multiple-Comparison test.