Hematopoietic Dysfunction in a Mouse Model for Fanconi Anemia Group D1

Susana Navarro, Nestor W. Meza, Oscar Quintana-Bustamante, José A. Casado, Ariana Jacome, Kimberly McAllister, Silvia Puerto, Jordi Surrallés, José C. Segovia, Juan A. Bueren

Research output: Contribution to journalArticleResearchpeer-review

85 Citations (Scopus)


We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2Δ27/Δ27 mutation). In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2Δ27/Δ27 mice, either young or adult. Additionally, a high incidence of spontaneous chromosomal instability was observed in Brca2Δ27/Δ27 bone marrow (BM) cells, but not in Brca2+/Δ27 or Fanca-/- BM cells. Although Brca2Δ27/Δ27 CFCs were not hypersensitive to ionizing radiation, a very severe hematopoietic syndrome was observed in irradiated Brca2Δ27/Δ27 mice. Conventional BM competition experiments showed a marked repopulation defect in Brca2Δ27/Δ27 hematopoietic stem cells (HSCs), compared to wild-type HSCs. Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2Δ27/Δ27 HSCs maintained in their natural physiological environment. The progressive repopulation of wild-type HSCs transplanted into unconditioned Brca2Δ27/Δ27 recipients is reminiscent of the somatic mosaicism phenomenon observed in a number of genetic diseases, including FA. The hematopoietic phenotype associated with the Brca2Δ27/Δ27 mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy. © 2006 The American Society of Gene Therapy.
Original languageEnglish
Pages (from-to)525-535
JournalMolecular Therapy
Publication statusPublished - 1 Oct 2006


  • Brca2
  • DNA repair
  • Fancd1
  • Fanconi anemia
  • competitive repopulation ability
  • genetic instability
  • hematopoiesis
  • hematopoietic stem cells
  • mitomycin C
  • self-renewal


Dive into the research topics of 'Hematopoietic Dysfunction in a Mouse Model for Fanconi Anemia Group D1'. Together they form a unique fingerprint.

Cite this