Lentiviral correction of early progenitors and phenotypical correction in FA KO mice.

(A) Southern blot analysis on CFU-S–derived colonies. Genomic DNA was obtained from spleen colonies digested with appropriate restriction enzymes and hybridized with probes recognizing the lenti-FANCA (left) or the lenti-FANCC (right) proviruses (see “Materials and methods”). All the colonies show a single band, indicating a single integration site. Colonies 1 to 11 were isolated from the same mouse and show a band of the same apparent molecular weight, thus suggesting a monoclonal origin. (B) Phenotypical correction in lentiviral-corrected Fanca^−/−and Fancc^−/−mice. Platelet counts were determined at 2-week intervals after the intraperitoneal (ip) administration of 0.3 mg/kg MMC. Lentiviral-corrected mice were protected against MMC toxicity for the duration of the experiment, but all knockout mice experienced severe hematological toxicity, leading most (4 of 6) of them to death within 6 weeks.