9 research outputs found
Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene
Fanconi anemia (FA) is an autosomal recessive chromosome instability
syndrome characterized by progressive bone marrow (BM) failure, skeletal
defects, and increased susceptibility to malignancy. FA cells are
hypersensitive to DNA cross-linking agents, oxygen and have cell cycle
abnormalities. To develop an animal model of the disease we generated mice
homozygous for a targeted deletion of exon 9 of the murine FA
complementation group C gene (fac). Mutant mice had normal neonatal
viability and gross morphology, but their cells had the expected
chromosome breakage and DNA cross-linker sensitivity. Surprisingly, male
and female mutant mice had reduced numbers of germ cells and females had
markedly impaired fertility. No anemia was detectable in the peripheral
blood during the first year of life, but the colony forming capacity of
marrow progenitor cells was abnormal in vitro in mutant mice. Progenitor
cells from fac knock-out mice were hypersensitive to interferon gamma.
This previously unrecognized phenotype may form the basis for BM failure
in human FA