Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage.

摘要: Fanconi anemia (FA) is a pleiotropic inherited disease that causes bone marrow failure in children. However, the specific involvement of FA genes hematopoiesis and their relation to (BM) still unclear. The increased sensitivity cells DNA cross-linking agents such as mitomycin C (MMC) diepoxybutane (DEB), including induction chromosomal aberrations delay G2 phase cell cycle, have suggested role for repair, cycle regulation, apoptosis. We previously reported cloning group gene (FAC) generation Fac mouse model. Surprisingly, -/- mice did not show any hematologic defects found patients. To better understand relationship functions BM failure, we analyzed vivo effect an FA-specific damaging agent mice. were be highly sensitive agents; acute exposure MMC produced marked hypoplasia degeneration proliferative tissues caused death within few days treatment. sequential, nonlethal doses progressive decrease all peripheral blood parameters This treatment targeted specifically compartment, with no on other tissues. pancytopenia resulted from reduction number early committed hematopoietic progenitors. These results indicate are involved physiologic response progenitor damage.