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. 2015 Sep 29;6:8186. doi: 10.1038/ncomms9186

Figure 4. The absence of Nr1i2 in Abcb11−/− deficient mothers rescues neonates.

Figure 4

(a) A heatmap of transcription factors, PPARγ, LXR and PXR (Nr1i2) in the liver revealed only PXR upregulation in Abcb11−/− mice. (b) Survival rate of neonates shown with respect to their maternal genotype, WT (green bar; n=2), Abcb11−/− (n=4), Nr1i2−/− (yellow bar; n=4) and Abcb11−/−/Nr1i2−/− (purple bar; n=4); n is the number of independent matings. All mice were congenic as defined by backcrossing at least 10 generations and SNP markers. (c) Serum bile acid concentrations were determined in animals of the following genotypes: WT (blue bar; n=15), Abcb11−/− (purple bar; n=18), Nr1i2−/− (brown bar; n=7), Abcb11−/−/Nr1i2−/− (grey bar; n=25). (d) Bile pool sizes in liver and small intestine including gall bladder were determined separately in the female mice of Abcb11−/− and Abcb11−/−/Nr1i2−/−. n=3. (e) Protein expression of hepatic transporters were measured by immunoblotting from total liver homogenates of Abcb11−/− (purple bar) and Abcb11−/−/Nr1i2−/− (grey bar) mice. Densitometry is on the right. (f) Protein expression of bile acid transporters on the apical and basolateral membranes were determined by immunoblotting in the ileal fragments of Abcb11−/− and Abcb11−/−/Nr1i2−/− mice. Densitometry is shown on the right. (g) Bile acid reabsorption in ileal fragment of small intestine was measured using a probe bile acid 14C-taurocholic acid. n=4–7. (black bar=WT, green bar=Abcb11−/− and blue bar=Abcb11−/−/Nr1i2−/−). (h) A schematic model showing the changes of ileal bile acid transporters involved in enterohepatic circulation in the Abcb11−/−/Nr1i2−/− female mice. Black single arrows indicate decreased protein expression, and red single arrows increased protein expression. Double black arrows indicate decreased bile acid transport. All experimental values are presented as mean±s.e.m. The height of the error bar=1 standard error. Statistical analysis was processed using two-tailed Student's t-test. **P<0.01; ***P<0.001; ****P<0.0001.