Loss of either FXR or SHP alone, or Fxr-/-Shp-/- double knock out mice resulted in cholestasis and liver injury as early as 3 weeks of age, and this dysfunction is linked to the dysregulation of bile acid homeostatic key genes, particularly Cyp7a1 (Anakk et al., 2011). The gene discussed is NR1H4; the disease is cholestasis.