Erythropoietic porphyria of the fox squirrel Sciurus niger

Uroporphyrin I is found in high concentration in the bones, teeth, blood, soft tissues, and urine of the fox squirrel, Sciurus niger. The concentration of uroporphyrin in fox squirrel spleen is much higher than in liver, kidney or bone marrow, probably because of accumulation from phagocytosed red cells. Bleeding causes a marked increase in the uroporphyrin concentration of red cells and spleen, and a 3-8-fold increase in uroporphyrin excretion. Urinary excretion of delta-aminolevulinic acid and porphobilinogen is not greater in fox squirrels than in nonporphyric gray squirrels. Sciurus carolinensis, used as controls. In all these characteristics, as well as in the previously demonstrated deficiency of the enzyme uroporphyrinogen III cosynthetase in red cells, the physiological porphyria of fox squirrels resembles congenital erythropoietic porphyria, a hereditary disease of man and cattle. For squirrels differ in showing no evidence of cutaneous photosensitivity or hemolytic anemia. Uroporphyrinogen III cosynthetase activity is present in fox squirrel bone marrow at 1/10 its concentration in gray squirrel marrow. The fox squirrel enzyme is much more unstable than the gray squirrel enzyme, which provides a possible explanation for its low activity and for the overproduction of uroporphyrin I. It is unlikely that the deficiency of cosynthetase is due to its inactivation by excessive amounts of uroporphyrinogen I synthetase, because activity of the latter enzyme is the same in blood from fox and gray squirrels.Fox squirrel porphyria provides a convenient model for studies of pathogenesis of human congenital erythropoietic porphyria.