Fanconi anaemia (FA) is a rare recessive disorder marked by developmental 
abnormalities, bone marrow failure, and a high risk for the development of 
leukaemia and solid tumours. The inactivation of FA genes, in particular FANCF, 
has also been documented in sporadic tumours in non-FA patients. To study 
whether there is a causal relationship between FA pathway defects and tumour 
development, we have generated a mouse model with a targeted disruption of the 
FA core complex gene Fancf. Fancf-deficient mouse embryonic fibroblasts 
displayed a phenotype typical for FA cells: they showed an aberrant response to 
DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, 
reduced survival, and an inability to monoubiquitinate FANCD2. Fancf homozygous 
mice were viable, born following a normal Mendelian distribution, and showed no 
growth retardation or developmental abnormalities. The gonads of Fancf mutant 
mice functioned abnormally, showing compromised follicle development and 
spermatogenesis as has been observed in other FA mouse models and in FA 
patients. In a cohort of Fancf-deficient mice, we observed decreased overall 
survival and increased tumour incidence. Notably, in seven female mice, six 
ovarian tumours developed: five granulosa cell tumours and one luteoma. One 
mouse had developed tumours in both ovaries. High-resolution array comparative 
genomic hybridization (aCGH) on these tumours suggests that the increased 
incidence of ovarian tumours correlates with the infertility in Fancf-deficient 
mice and the genomic instability characteristic of FA pathway deficiency.