The Fanconi anemia (FA) core complex member FANCM remodels synthetic replication 
forks and recombination intermediates. Thus far, only one FA patient with FANCM 
mutations has been described, but the relevance of these mutations for the FA 
phenotype is uncertain. To provide further experimental access to the FA-M 
complementation group we have generated Fancm-deficient mice by deleting exon 2. 
FANCM deficiency caused hypogonadism in mice and hypersensitivity to 
cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying 
other FA mouse models. However, Fancm(Delta2/Delta2) mice also showed unique 
features atypical for FA mice, including underrepresentation of female 
Fancm(Delta2/Delta2) mice and decreased overall and tumor-free survival. This 
increased cancer incidence may be correlated to the role of FANCM in the 
suppression of spontaneous sister chromatid exchanges as observed in MEFs. In 
addition, FANCM appeared to have a stimulatory rather than essential role in 
FANCD2 monoubiquitination. The FA-M mouse model presented here suggests that 
FANCM functions both inside and outside the FA core complex to maintain genome 
stability and to prevent tumorigenesis.