Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol.
Blood
; 116(24): 5140-8, 2010 Dec 09.
Article
em En
| MEDLINE
| ID: mdl-20826722
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 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.
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Base de dados:
MEDLINE
Assunto principal:
Estilbenos
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
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Anemia de Fanconi
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Sistema Hematopoético
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article