Natural Variation in Expression of Urea Cycle Genes

The urea cycle converts waste nitrogen into urea and in mammals, the primary known function is to protect the brain from the toxic effects of ammonia. Northern blots of mouse tissues showed N‐acetyglutamate synthase (NAGS) expression in spleen, testis, and, as expected, in the liver and intestine. Western blotting confirmed the presence of NAGS protein in all four tissues. The expression of three urea cycle genes was examined in 14 mouse tissue using RT PCR. Significant expression was seen in the kidney, ovary, spleen, testis and stomach. Expression of the corresponding proteins was dependent on the strain of mice used for harvesting tissues. This suggests a natural variation in expression of the urea cycle and presumably other pathways, that could be important for adaptation to a changing environment. We hypothesize that extrahepatic expression of urea cycle genes may be important for arginine biosynthesis. In organisms that dispose of waste nitrogen by other means, the purpose of the urea cycle is not well understood. We have identified the urea cycle genes in zebrafish and are examining their expression in developing embryos to better understand extrahepatic roles of the urea cycle. Knowledge of the underlying reasons for the natural variability in urea cycle gene expression could be important for understanding the disease progression and side effects of medications in individual patients.