Figure 1.
Targeted disruption of the murine Fabp6 gene.
(A) Structure of wild-type (wt) and disrupted Fabp6 alleles. The targeting vector was designed to replace the region of the Fabp6 gene encompassing exons 2 and 3 with the neo resistance (neor) gene cassette. X, Xba I site. (B) RNA blot of small intestine RNA from Fabp6+/+ and Fabp6−/− mice probed with [32P]-labeled ilbp cDNA. (C) Protein blot of small intestine homogenates from Fabp6+/+ and Fabp6−/− mice probed with antiserum to murine ilbp.
Table 1.
Plasma chemistry.
Table 2.
Bile acid pool size and excretion rate.
Figure 2.
Absorption and tissue distribution of orally administered [3H]TCA in Fabp6+/+ and Fabp6−/− mice.
(A) Retained and excreted [3H]TCA at 24 h after oral administration. Values shown are mean±SEM (males, n = 4–5; females, n = 5–6). (B) Tissue distribution of the retained [3H]TCA in Fabp6+/+ and Fabp6−/− mice. *P<0.05, **P<0.02, ***P<0.005, vs. wild-type of the same sex.
Figure 3.
Transport of bile acids in everted gut sacs.
(A) Amount of TCA accumulated in the serosal fluid after a 30 min incubation of gut sacs from the proximal one-third and distal one-third portions of the small intestine of male Fabp6+/+ (n = 4), female Fabp6+/+ (n = 3–4) mice (black bars), male Fabp6−/− (n = 4) and female Fabp6−/− (n = 5) mice (white bars). (B) Amount of TCA accumulated in the gut sac tissue at the end of the assay incubation period. *P<0.025, **P<0.01, vs. wild-type of the same sex.
Figure 4.
Hepatic cholesterol concentration and enzyme activities of Fabp6+/+ (black bars) and Fabp6−/− (white bars) mice.
(A) Unesterified cholesterol concentration and (B) Cholesteryl ester concentration, (n = 3). (C) Relative cyp7a1 activity (n = 5). (D) Relative HMGR activity (n = 5). Groups are compared relative to male Fabp6+/+ mice.
Figure 5.
Survey of gene expression in the liver.
qPCR analysis of liver RNA from Fabp6+/+ (black bars) and Fabp6−/− (white bars) mice were done in duplicates. The abundance (mean ± SEM) of target mRNAs was normalized to internal standards and expressed relative male wild-type mice. *P<0.05, vs. wild-type.
Figure 6.
Survey of gene expression in the small intestine.
(A) qPCR analysis of RNA from small intestines of Fabp6+/+ (black bars) and Fabp6−/− (white bars) were done in duplicates. The normalized abundance (mean±SEM) of target mRNAs is expressed relative to male Fabp6+/+ mice. P<0.05, vs. wild-type of the same sex. (B) Protein blots of small intestine homogenates of Fabp6+/+ and Fabp6−/− mice were probed with antisera to ilbp, asbt and L-FABP.