Hematopoietic compartment of Fanconi anemia group C null mice contains fewer lineage-negative CD34(+) primitive hematopoietic cells and shows reducedreconstitution ability
M. Carreau et al., Hematopoietic compartment of Fanconi anemia group C null mice contains fewer lineage-negative CD34(+) primitive hematopoietic cells and shows reducedreconstitution ability, EXP HEMATOL, 27(11), 1999, pp. 1667-1674
Fanconi anemia (PA) is a complex recessive genetic disease that causes bone
marrow failure in children. The mechanism by which the gene for FA group C
(Fancc) impinges on the normal hematopoietic program is unknown. Here we d
emonstrate that the bone marrow from Fancc-/- mice have reduced ability for
primary and secondary long-term reconstitution of myeloablated recipients
compared to wild-type or heterozygous mice, indicating that the Fancc gene
product is required for the maintenance of normal numbers of hematopoietic
stem cells. Long-term and secondary transplant studies suggested that there
also were qualitative changes in their developmental potential. Consistent
with the reduction in reconstitution, flow cytometric analysis of the prim
itive subfractions of hematopoietic cells obtained from the bone marrow of
Fancc-/- mice demonstrated that they contained 40 to 70% fewer lineage-nega
tive (Lin(-))Thy1.2(-/low)Sca1(+)c-Kit(+)CD34(+) cells compared to controls
. In contrast, the number of Lin(-)Thy1.2(-/low)Sca1(+)c-Kit(+)CD34(-) cell
s was comparable to that of wild-type mice. The differential behavior of Li
n(-)Thy1.2(-/low)Sca1(+)cKit(+) CD34(+) and Lin(-)Thy1.2(-/low)Sca1(+)c-Kit
(+)CD34(-) subfractions also was observed in mice treated with the DNA cros
slinking agent mitomycin C (MMC). Fancc-/- mice treated with MMC had an 92%
reduction of CD34(+) cells as compared to Fancc+/+ mice. The number of CD3
4(-) cells only was reduced about 20%. These results suggest that the Fancc
gene may act at a stage of primitive hematopoietic cell development identi
fied by CD34 expression. (C) 1999 International Society for Experimental He
matology. Published by Elsevier Science Inc.