Journal of Experimental Medicine, Vol 156, 398-414, Copyright © 1982 by Rockefeller University Press
Erythroleukemia induction by Friend leukemia virus. A host gene locus controlling early anemia or polycythemia and the rate of proliferation of late erythroid cells
T Shibuya, Y Niho and TW Mak
This report confirms that the Fv-5 locus controls the types of
erythropoiesis induced by Friend erythroleukemia virus (FLV) (21) and
extends the study to investigate the mode of action of this locus. With the
use of FLV obtained by a variety of procedures, we showed that the
polycythemia spleen focus-forming component (SFFVp) was responsible for the
contrasting changes of hematocrits observed in FV-Pp (polycythemia
strain)-infected DBA/2 (Fv-5pp) or CBA (Fv-5aa) mice. These changes in
hematocrits were found to be a direct result of the rise in circulating
reticulocytes and erythrocytes in DBA/2 mice and a corresponding drop of
these erythroid cells in CBA mice 2 wk after infection. Examination of the
FV-P-induced cellular changes indicated that dramatic increase in
erythropoietin (epo)-independent erythroid precursor (CFU-E*) cells was
detected in the spleens and marrow of both strains of mice. The epo
responsiveness of the CFU-E in the uninfected and FV-P-infected CBA and
DBA/2 mice was also very similar. Similar to FLV-infected DBA/2 mice, the
FV-P-infected CBA mice also developed tumorogenic cells (CFU-FV) relatively
early after infection (4-6 wk). Study of the physiological and pathological
changes in the marrows and spleens of these infected mice indicated that
significant differences were found in the spleens of the two strains of
mice. The percent of reticulocytes in the spleen cells of CBA mice remained
between 10 and 20%, and level of the DBA/2 mice increased to approximately
50%. This higher rate of erythropoiesis was also reflected in the
significantly higher rate of uptake of 59Fe in the spleens of the DBA/2
mice. These results suggest that the Fv-5 locus might control the
hematocrit levels of these mice by regulating the rates of erythropoiesis
in the spleen levels of these mice, probably by affecting the rate of
proliferation of an erythroid cell or cells. The erythroid cell(s) affected
is likely to be more mature than the erythroid progenitor, CFU-E, as the
levels of CFU-E in these two strains of mice were similar. The hypothesis
that Fv-5 may control the rates of proliferation of a late erythroid
(cell(s) is also supported by the significantly higher spleen weights found
in the infected DBA/2 (approximately 2.5 g/spleen) mice than in the CBA
(approximately 1 g/spleen) strain.
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