Chronic liver disease is triggered by taurine transporter knockout in the mouse

SPECIFIC AIMSIn view of the important role of taurine in liver physiology and in cell protection against various types of injury, the liver phenotype was examined in taurine transporter-deficient mice (taut−/−). The findings support the view that taurine deficiency can trigger hepatitis and liver fibrosis, probably due to a diminished antioxidant defense, up-regulation of inflammatory cytokines and mitochondrial dysfunction.PRINCIPAL FINDINGS1. Taurine levels are strongly decreased in Kupffer and sinusoidal endothelial cells, but not in parenchymal cells of (taut−/−) miceHomozygous disruption of the taut gene resulted in a decrease in taurine levels in skeletal and heart muscles by ∼99%, whereas hepatic taurine levels were diminished by 70% in adult (taut−/−) and by 30% in (taut+/−) mice. Immunoelectron microscopy revealed an almost complete depletion of taurine in Kupffer and sinusoidal endothelial cells, but not in hepatic parenchymal cells of (taut−/−) mice.2. (taut−/−) and (taut+/−) mice develop moder...