Disruption of the ileal BA transporter gene Slc10a2

<p><b>activates enzymes in BA synthesis.</b> (A) mRNA levels of cholesterol 7α-hydroxylase (Cyp7a1) in livers of wt, <i>Slc10a2+/−</i> and <i>Slc10a2−/−</i> animals. (B) Cyp7a1 enzymatic activity in pooled microsomal samples from livers of wt, <i>Slc10a2+/−</i> and <i>Slc10a2−/−</i> animals. Results shown are mean of two analyses. (C) Protein levels of Cyp7a1 in livers of wt, <i>Slc10a2+/−</i> and <i>Slc10a2−/−</i> mice determined in pooled microsomal samples by immunoblot using a Cyp7a1-specific antibody. 20 µg and 40 µg of protein were used per sample, respectively. The results are representative of three separate immunoblots. Note the loading order of the samples. (<b>D</b>) Serum levels of the Cyp7a1 activity marker 7α-hydroxy-4-cholesten-3-one (C4) were assayed as an indirect measure of Cyp7a1 enzymatic activity in pooled serum samples of wt, <i>Slc10a2+/−</i> and <i>Slc10a2−/−</i> animals. Data show mean of two separate measurements. (<b>E</b>) hepatic mRNA levels of 12α-hydroxylase (Cyp8b1), and (<b>F</b>) hepatic small heterodimer partner (Shp) mRNA levels of wt, <i>Slc10a2+/−</i> and <i>Slc10a2−/−</i> mice. mRNA levels for the wt mice were normalized to 1. Data are expressed as mean ± standard error (SEM) for the mRNA analysis. wt littermates (n = 10), <i>Slc10a2+/−</i> (n = 9) and <i>Slc10a2−/−</i> (n = 10) for A-F. Significances of differences between groups was tested by Dunnetts test; a p-value < <0.01 is denoted **.