Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol

Qing-Shuo Zhang, Laura Marquez-Loza, Laura Eaton, Andrew W. Duncan, Devorah Goldman, Praveen Anur, Kevin Watanabe-Smith, R. Keaney Rathbun, William Fleming, Grover C. Bagby, Markus Grompe

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2-/- mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit +Sca-1+Lineage- (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2-/- KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2-/- mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2-/- KSL cells in quiescence, improved the marrow micro-environment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2-/- bone marrow cells. We conclude that Fancd2-/- mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.

Original languageEnglish (US)
Pages (from-to)5140-5148
Number of pages9
JournalBlood
Volume116
Issue number24
DOIs
Publication statusPublished - Dec 9 2010

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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