OBJECTIVE: Fanconi anemia (FA) is a genetically heterogeneous disorder 
associated with defects in at least eight genes. The biochemical function(s) of 
the FA proteins are unknown, but together they define the FA pathway, which is 
involved in cellular responses to DNA damage and in other cellular processes. It 
is currently unknown whether all FA proteins are involved in controlling a 
single function or whether some of the FA proteins have additional roles. The 
aim of this study was 1) to determine whether the FA group A and group C genes 
have identical or partially distinct functions, and 2) to have a better model 
for human FA.
MATERIALS AND METHODS: We generated mice with a targeted mutation in fanca and 
crossed them with fancc disrupted animals. Several phenotypes including 
sensitivity to DNA cross linkers and ionizing radiation, hematopoietic colony 
growth, and germ cell loss were analyzed in fanca-/-, fancc-/-, fanca/fancc 
double -/-, and controls.
RESULTS: Fibroblast cells and hematopoietic precursors from fanca/fancc 
double-mutant mice were not more sensitive to MMC than those of either single 
mutant. fanca/fancc double mutants had no evidence for an additive phenotype at 
the cellular or organismal level.
CONCLUSIONS: These results support a model where both FANCA and FANCC are part 
of a multi-protein nuclear FA complex with identical function in cellular 
responses to DNA damage and germ cell survival.