Fanconi anaemia (FA) is a rare genetic disease characterised by life-threatening anaemia and reduced fertility. The mechanism underlying reduced fertility in FA patients is not understood, however it is known that meiosis is essential for fertility to ensure correct chromosome segregation. FANCM, a translocase protein part of the FA pathway, binds to DNA branched structures (e.g. stalled replication forks), which are especially prevalent during S-phase replication and meiotic crossovers. FANCM recognises and binds to these DNA branched structures with high affinity to maintain genome stability and initiate DNA damage repair. FANCM mutations have previously been shown to play a role on fertility and meiosis in Arabidopsis thaliana and fission yeast. Using Fancm-deficient mice, we aim to investigate the role of FANCM in fertility and meiosis.
We have Fancm mouse models genetically edited in two different strain backgrounds to investigate genetic linkage analysis to measure recombination by identifying single nucleotide polymorphisms (SNPs) between two strains. Immunofluorescent chromosome meiotic slides were also performed to investigate whether FANCM interacts meiosis-specific proteins.
We found that Fancm–/– mice are not significantly different in body weight but have reduced testis (p<0.0001) and epididymis (p<0.01) weight. We also observed decreased sperm motility (p<0.01), progressivity (p<0.01) and reduced daily sperm production (p<0.05). From our linkage studies, we detected an increase in recombination in Fancm-/- mice, suggesting that the reduced fertility could be due to a hyper-recombination phenotype. Homozygous mutations in FANCM have been shown to cause infertility in patients. Our data suggest that FANCM could have a role in meiosis that affects the fertility in our mouse model. Our work will provide insight into how FANCM can maintain genome stability in a mouse model.