Progressive attrition of HSCs underlies BMF in FA. (A) The progressive decline of HSC numbers in FA patients leads to BMF early in life. The HSC defect is likely to start in utero. (B) Fanconi-deficient mice do not recapitulate the main feature of FA. For this reason, their usefulness as disease models has been questioned. However, FA-deficient mice do display a quantifiable defect in their HSC pool as well as reduced ability to reconstitute blood production in irradiated recipients, which is also present before birth. Even in the absence of BMF, it would be interesting to see if Fanconi-deficient mice display age-dependent attrition in the quality of their HSC pool, as has been observed for other DNA repair–deficient mice.