Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity 
to DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA 
cell death, chromosome breakage, and accumulation in the G2 phase of the cell 
cycle. Recently, Fanconi anemia complementation group C (fac) gene knock-out 
mice have been developed, and SV40-transformed fibroblasts were established from 
fac homozygous knock-out (-/-), heterozygous (+/-), and wild-type mice (+/+). 
MMC sensitivity of these cell lines was assessed by three methods: 
colony-formation assay in the presence of MMC, chromosome breakage, and cell 
cycle analysis to detect G2 phase arrest. The fac knock-out fibroblasts (-/-) 
showed a significantly higher sensitivity to MMC than did fibroblasts from 
wild-type (+/+) or heterozygous (+/-) mice (three experiments). In addition, we 
analyzed hematopoietic progenitor colony assays of bone marrow cells from fac 
knock-out (-/-) and heterozygous (+/-) mice. CFU-E, BFU-E, and CFU-GM colony 
formation from fac nullizygous mouse progenitors was markedly diminished by MMC 
when compared to growth of progenitors from heterozygous mice. These results 
show that fac knock-out mouse cells mimic the behavior of human FA-C patient 
cells in terms of MMC hypersensitivity. The fac knock-out mouse may be used to 
model some aspects of human FA and should be useful for understanding the 
function of the FAC protein.