Temporal replacement of donor erythrocytes and leukocytes in nonanemic
W44J/W44J and severely anemic W/Wv mice
JE Barker, J Greer, S Bacon and ST Compton
Jackson Laboratory, Bar Harbor, ME 04609.
The dominant white spotting, W, locus in the mouse encodes Kit, a receptor
molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete
hematopoietic cells by an as yet unknown mechanism, but one that presumably
affects the early progenitors of all cell lineages. To examine cell
lineage-specific changes caused by different W mutations, we injected
genetically marked normal marrow cells into mutant mice and monitored
repopulation kinetics. In the present report, we compare repopulation of
the various peripheral blood cells in nonanemic W44J/W44J and severely
anemic W/Wv mice administered increasing increments of donor cells. At all
doses of cells tested, donor erythrocyte repopulation precedes leukocyte
repopulation regardless of the recipient phenotype. There is, in fact,
little difference in the rate or extent of nonerythroid repopulation in
W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells.
The fact that donor cells rapidly replace erythrocytes, even in the
nonanemic W44J/W44J host, while other cell lineages become donor type more
slowly provides further evidence that mutations at the W locus are
especially damaging to erythrocyte progenitors. We suggest that host
nonerythroid hematopoietic cells compete with normal cells, probably at the
level of early progenitors rather than at the level of the totipotent
hematopoietic stem cell. The fact that successively higher doses of donor
cells do not markedly alter nonerythroid repopulation kinetics implies that
it may be possible to maximize autologous therapeutic marrow
transplantation.
Volume 78,
Issue 6,
pp. 1432-1437,
09/15/1991
Copyright © 1991 by The American Society of Hematology
