Retroviral-mediated transduction of the fanconi anemia C complementing (FACC) gene in two murine transplantation models.

Fanconi anemia (FA) is a well-known genetic syndrome manifested by bone marrow failure, variable physical anomalies, and cancer susceptibility. This disorder is marked by genotypic and phenotypic heterogeneity and consists of four distinct complementation groups A, B, C, and D. The defective gene responsible for the C group of FA, FACC, was identified by cDNA complementation cloning, and we have recently proposed a trial of gene therapy for group C FA. No animal model yet exists for FA. Consequently, we have studied the effects of constitutive expression of human FACC in two murine transplantation models. In the first model, we demonstrated transduction of FACC to reconstituting stem cells of mutant W/WV mice. In the second model, we demonstrated transduction of FACC to hematopoietic cells transplanted to the bone marrows and spleens of non-myeloablated BALB/c mice. Our data suggest that retroviral-mediated transfer of the normal human FACC cDNA to hematopoietic progenitor and stem cells of mice is feasible and not associated with direct harmful effects to the hematopoietic organ.