Ineffective hematopoiesis in folate-deficient mice.
A folate-free amino acid-based diet provided an opportunity to characterize the effects of folate depletion on growth, tissue folate levels, and hematopoiesis of mice under well-standardized conditions. Weanling mice were fed a folate-free, amino acid-based diet supplemented with either 0 or 2 mg folic acid/kg diet for 35 to 48 days. Folate concentrations were decreased in liver, kidney, serum, and erythrocytes in mice fed the folate-free diet. The folate-deficient mice had anemia, reticulocytopenia, thrombocytopenia, and leukopenia, all of which reverted to normal after folic acid was reintroduced to the diet. Hematopoietic organs of folate-deficient mice had alterations that were similar to those seen in folate-deficient humans except that in mice, the hyperplasia of hematopoietic tissue occurred in the spleen rather than in the marrow. Ferrokinetic studies showed a normal 59Fe-transferrin half-life, but the percentage of 59Fe-incorporation into red blood cells at 48 hours was markedly subnormal. The number of committed hematopoietic progenitors at the stages of erythroid colony-forming units (CFUs), megakaryocyte CFUs, and granulocyte-macrophage CFUs were all increased in folate-deficient mice. However, the progeny of these progenitors was markedly decreased in folate-deficient mice. Thus, the folate-deficient mice had "ineffective hematopoiesis" leading to pancytopenia, and they therefore provide a murine model of megaloblastic anemia.
Bills
N D
ND
Department of Nutrition, University of California, Davis 95616-8669.
Koury
M J
MJ
Clifford
A J
AJ
Dessypris
E N
EN
D000749:Anemia, Megaloblastic / Q000209:etiology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D005494:Folic Acid Deficiency / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D006410:Hematopoiesis; D051379:Mice; D013154:Spleen / Q000473:pathology