Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Fancf-deficient mice are prone to develop ovarian tumors. Bakker ST et al. Fanconi Anemia (FA) is a rare recessive disorder marked by developmental abnormalities, bone marrow failure, and a high risk for the development of leukemia and solid tumors. The inactivation of FA genes, in particular FANCF, has also been documented in sporadic tumors in non-FA patients. To study whether there is a causal relationship between FA pathway defects and tumor 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 crosslinking 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 tumor incidence. Notably, in 7 female mice 6 ovarian tumors developed, 5 granulosa cell tumors and one luteoma. One mouse had developed tumors in both ovaries. High-resolution array comparative genomic hybridization (aCGH) on these tumors suggest that the increased incidence of ovarian tumors correlates with the infertility in Fancf-deficient mice and the genomic instability characteristic for FA pathway deficiency. Copyright 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.