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Next Article 
Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 1-8
Loss of FancC Function Results in Decreased Hematopoietic Stem
Cell Repopulating Ability
Laura S. Haneline,
Troy A. Gobbett,
Rema Ramani,
Madeleine Carreau,
Manuel Buchwald,
Mervin C. Yoder, and
D. Wade Clapp
From the Department of Pediatrics, Herman B Wells Center for
Pediatric Research and the Departments of Microbiology/Immunology and
Biochemistry and Molecular Biology, Indiana University School of
Medicine, Indianapolis, IN; and the Department of Genetics, The
Hospital for Sick Children, Toronto; and the Department of Molecular
and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.
Fanconi anemia (FA) is a complex genetic disorder characterized by
progressive bone marrow (BM) aplasia, chromosomal instability, and
acquisition of malignancies, particularly myeloid leukemia. We used a
murine model containing a disruption of the murine homologue of
FANCC (FancC) to evaluate short- and long-term
multilineage repopulating ability of FancC  / cells in
vivo. Competitive repopulation assays were conducted where "test"
FancC / or FancC +/+ BM cells (expressing
CD45.2) were cotransplanted with congenic competitor cells (expressing
CD45.1) into irradiated mice. In two independent experiments, we
determined that FancC / BM cells have a profound decrease
in short-term, as well as long-term, multilineage repopulating ability.
To determine quantitatively the relative production of progeny cells by
each test cell population, we calculated test cell contribution to
chimerism as compared with 1 × 105 competitor cells. We
determined that FancC / cells have a 7-fold to 12-fold
decrease in repopulating ability compared with FancC +/+
cells. These data indicate that loss of FancC function results in reduced in vivo repopulating ability of pluripotential hematopoietic stem cells, which may play a role in the development of the BM failure
in FA patients. This model system provides a powerful tool for
evaluation of experimental therapeutics on hematopoietic stem cell function.
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