| First Author | Zhang QS | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 24 | Pages | 5140-8 |
| PubMed ID | 20826722 | Mgi Jnum | J:167414 |
| Mgi Id | MGI:4868184 | Doi | 10.1182/blood-2010-04-278226 |
| Citation | Zhang QS, et al. (2010) Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. Blood 116(24):5140-8 |
| abstractText | 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 microenvironment, 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. |
