DISRUPTION OF THE ADENOSINE-DEAMINASE GENE CAUSES HEPATOCELLULAR IMPAIRMENT AND PERINATAL LETHALITY IN MICE

We have generated mice with a null mutation at the Ada locus, which en codes the purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4 ), ADA-deficient fetuses exhibited hepatocellular impairment and died perinatally, Their lymphoid tissues were not largely affected, Accumul ation of ADA substrates was detectable in ADA-deficient conceptuses as early as 12.5 days postcoitum, dramatically increasing during late in utero development, and is the likely cause of liver damage and fetal death. The results presented here demonstrate that ADA is important fo r the homeostatic maintenance of purines in mice.