Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression

Blood. 2004 Apr 1;103(7):2522-9. doi: 10.1182/blood-2003-07-2439. Epub 2003 Nov 20.

Abstract

The Runx1/core binding factor-beta (CBFbeta) transcriptional complex is required for the establishment of hematopoiesis during development. Despite its critical role during development, a detailed analysis of Runx1 expression within specific lineages and developmental stages of the adult hematopoietic system is lacking. To address this, we have developed a Runx1-green fluorescent protein (GFP) knock-in mouse. We show that Runx1 is expressed in several hematopoietic lineages, including myeloid, B-lymphoid, and T-lymphoid cells. By contrast, Runx1 is weakly expressed in early erythroid cells, and its expression is rapidly extinguished during later stages of erythropoiesis. Runx1 expression is induced during early B-cell development and is expressed at a uniform level during all subsequent stages of B-cell development. Within the thymus, Runx1 is expressed at the highest level in CD4-CD8- double-negative thymocytes. In peripheral T cells, Runx1 is differentially expressed, with CD4+ T cells expressing 2- to 3-fold higher levels of Runx1 than CD8+ cells. Taken together, these findings indicate that although widely expressed in the hematopoietic system, the expression of Runx1 is regulated in a cell type- and maturation stage-specific manner. In addition, the Runx1-IRES-GFP knock-in mouse strain should prove valuable for investigation of Runx1 function in adult hematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / physiology
  • Core Binding Factor Alpha 2 Subunit
  • DNA Primers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation
  • Genotype
  • Green Fluorescent Proteins
  • Hematopoiesis / physiology*
  • Humans
  • Luminescent Proteins / genetics
  • Lymph Nodes / physiology
  • Lymphocyte Subsets / physiology
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction / methods
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA Primers
  • DNA-Binding Proteins
  • Luminescent Proteins
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Runx1 protein, mouse
  • Transcription Factors
  • Green Fluorescent Proteins