Loss of negative feedback regulation in bile acid synthesis in Cyp8b1-knockout mice. While both wild-type (WT) and mutant mice produce chenodeoxycholic acid (CDCA), Cyp8b1 knockouts lack cholic acid (CA). Contrary to the expectation from the redundant negative feedback mechanisms mediated by the farnesoid X receptor (FXR) and small heterodimer partner (SHP), and also other factors in WT mice, Cyp7a1 expression in the knockout mice is actually increased. The mechanisms whereby the loss of CA results in the loss of negative feedback are unknown.