A Novel Cysteine Sulfinic Acid Decarboxylase Knock-Out Mouse: Comparison Between Newborn and Weanling Mice

Abstract

We developed a novel cysteine sulfinic acid decarboxylase knockout mouse (CSAD KO) to investigate the critical roles of taurine. The absence of the CSAD gene was confirmed using Southern, northern and western blotting; homozygous (CSAD^−/−) and heterozygous (CSAD^+/-) animals were identified using PCR. Plasma taurine concentrations were decreased by 86 % in CSAD^−/− animals. Reproductive performance was poor in the second and later CSAD^−/− generations but was restored by supplementing the drinking water with 0.05 % taurine. Taurine concentrations at postnatal day 1 (PD1) in generation 1 (G1) CSAD^−/− were close to normal presumably due to taurine transport through the placenta from the CSAD^+/− dam. In contrast, taurine concentrations in the brain and liver of G2, G3, and G4 CSAD^−/− were very low at birth. At 1 month of age (1 M), 1 week after weaning, the G1 CSAD^−/− taurine concentration in the liver decreased to the same level as G2, G3, and G4 CSAD^−/−. Taurine concentrations in all CSAD^−/− at 1 M were reduced to 44 % of WT in the brain and 5 % in the liver. Taurine supplementation restored brain levels to 76 % of WT but had little effect on the liver. Gene expression in CSAD^−/− brain and liver was compared to WT at PD1 and 1 M. Expression of the prolactin receptor and lactoferrin genes was decreased in CSAD^−/− at both PD1 and 1 M. Metabolic genes including serine dehydratase and uridine phosphorylase 2 were increased significantly at PD1 but not at 1 M. An oxidative stress gene, glutathioneperoxidase 3 was increased in CSAD KO^−/− at both PD1 and 1 M. Expression of taurine metabolism genes, cysteine dioxygenase (Cdo), cysteamine dioxygenase and the taurine transporter (TauT) were unaffected at PD1. At 1 M, however, TauT in CSAD^−/− liver was increased twofold, while Cdo was decreased compared to WT. These data indicate that the CSAD KO mouse is a powerful model for exploring the role of taurine deficiency in various disorders especially since the requirement for taurine can be supplied in food or water.