Defective gastrointestinal recovery after irradiation in W/Wv mice

W/Wv mice are white, sterile, and have macrocytic anemia, all due to defective function of pertinent stem cell compartments. Sterility and coat color reflect stem cell failure during embryogenesis, while anemia results from a defective hematopoietic stem cell system which is active throughout life. Studies of radiation damage and recovery were undertaken to determine if the stem cell compartment of the intestinal mucosa, also active throughout life, is likewise affected. W/Wv mice "cured" of their hematopoietic defect, and normal littermates were exposed to 1,250 rads of whole-body irradiation. Mean survival time of controls was 8.4 plus or minus 0.31 days compared to only 5.85 plus or minus 0.18 days (P = LESS THAN0.001) FOR W/Wv. Incorporation of 3HTdR into mucosal cells of controls was minimum 2 days after exposure and exceeded nonirradiated levels by day 3, W/Wv values were lower than controls on days 2-4 and never significantly exceeded nonirradiated values. Changes in gut weight followed the same pattern. These studies suggest that the W/Wv defect involves stem cells of the gut and that the defect is a failure to proliferate and/or differentiate.