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

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

Authors

  • Talebian L
  • Li Z
  • Guo Y
  • Gaudet J
  • Speck ME
  • Sugiyama D
  • Kaur P
  • Pear WS
  • Maillard I
  • Speck NA

Journal

Blood

Publication Data

January 1, 2007

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

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