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T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFbeta dosage.

Blood | Jan 1, 2007

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFbeta. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFbeta levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFbeta levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFbeta levels, and were virtually absent when CBFbeta levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4- CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFbeta threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.

Pubmed ID: 16940420 RIS Download

Mesh terms: Alleles | Animals | Bone Development | Cell Lineage | Colony-Forming Units Assay | Core Binding Factor alpha Subunits | Core Binding Factor beta Subunit | Granulocytes | Hematopoiesis | Liver | Megakaryocytes | Mice | Mice, Inbred C57BL | Mice, Knockout | Phenotype | Radiation Chimera | Spleen | T-Lymphocyte Subsets | Thymus Gland

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Associated grants

  • Agency: NCI NIH HHS, Id: CA 23108
  • Agency: NIAID NIH HHS, Id: R01 AI047833
  • Agency: NCI NIH HHS, Id: R01 CA75611
  • Agency: NIAMS NIH HHS, Id: T32 AR07576
  • Agency: NCI NIH HHS, Id: P30 CA023108
  • Agency: NIAMS NIH HHS, Id: T32 AR007576
  • Agency: NCI NIH HHS, Id: R01 CA075611

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