Figure 8: Mice expressing the K68R SHP mutant have exacerbated cholestatic symptoms upon biliary insults.

(a–c) BA overload experiments. (a) Mice were fed 0.5% CA chow for 5 days and hepatic and serum BA levels were determined. Values represent mean±s.e.m. (b) The mRNA levels of the indicated hepatic genes were measured. Values represent mean±s.e.m. Statistical significance was determined by the Student’s t-test, (n=5 mice, *P<0.05, **P<0.005, and NS, statistically not significant) (a,b). (c) Liver sections were stained and macrophages detected as in Fig. 7g. Scale bar, 100 μm. (d–h) ANIT experiments. (d) Pictures of serum and gall bladders from control and ANIT-treated mice expressing SHP or the K68R mutant. (e) Hepatic, serum, intestinal and gall bladder BA levels, serum AST levels and total bilirubin levels. Values represent mean±s.e.m. (f) BA composition in the liver. Values represent mean±s.e.m. (g) The mRNA levels of the indicated genes in liver and intestine were measured. Values represent mean±s.e.m. Statistical significance was determined by the Student’s t-test, (n=5 mice, *P<0.05, **P<0.005 and NS, statistically not significant) (e–g). (h) Liver sections were stained and macrophages detected as in Fig. 7g. Scale bar, 50 μm (F4/80), 250 μm and 100 μm (H&E).