Development of a Novel Cysteine Sulfinic Acid Decarboxylase Knockout Mouse: Dietary Taurine Reduces Neonatal Mortality

Abstract

We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption of the CSAD gene was verified by Southern, Northern, and Western blotting. HPLC indicated an 83% decrease of taurine concentration in the plasma of CSAD - / - . Although CSAD - / - generation (G)1 and G2 survived, offspring from G2 CSAD - / - had low brain and liver taurine concentrations and most died within 24 hrs of birth. Taurine concentrations in G3 CSAD - / - born from G2 CSAD - / - treated with taurine in the drinking water were restored and survival rates of G3 CSAD - / - increased from 15% to 92%. The mRNA expression of CDO, ADO, and TauT was not different in CSAD - / - compared to WT and CSAD mRNA was not expressed in CSAD - / - . Expression of Gpx 1 and 3 was increased significantly in CSAD - / - and restored to normal levels with taurine supplementation. Lactoferrin and the prolactin receptor were significantly decreased in CSAD - / - . The prolactin receptor was restored with taurine supplementation. These data indicated that CSAD KO is a good model for studying the effects of taurine deficiency and its treatment with taurine supplementation.