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Ineffective hematopoiesis in folate-deficient mice
ND Bills, MJ Koury, AJ Clifford and EN Dessypris
Department of Nutrition, University of California, Davis 95616-8669.
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.
Volume 79,
Issue 9,
pp. 2273-2280,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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