The active DNA-repair response in bone marrow cells indicates that even in the absence of FANCD2, there is an alternative repair response to both endogenous and ethanol-derived aldehydes. However, our previous work has shown that Aldh2−/−Fancd2−/− mice lose the ability to maintain blood production5,6. To determine whether this is due to the accumulation of damaged DNA, we examined haematopoietic cells for evidence of broken chromosomes. One marker of genetic instability is the formation of micronuclei, which are formed from lagging or broken chromosomes. Micronuclei are easily quantified in normochromic erythrocytes (NCEs) in vivo, because they persist following enucleation (Fig. 2a, Extended Data Fig. 1c). There is a significant increase in the proportion of NCEs with micronuclei in both Aldh2−/− (2.9-fold) and Fancd2−/− (1.9-fold) mice compared to wild-type controls, but the increase is much larger in Aldh2−/−Fancd2−/− mice (9.5-fold, Fig. 2b). These micronuclei could represent genomic instability during blood production. We therefore examined cells in metaphase obtained directly from the bone marrow of these mice with multiplex fluorescence in situ hybridization (M-FISH). More than 10% of Aldh2−/−Fancd2−/− bone-marrow cells carried chromosomal
