The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development

Eur J Immunol. 2000 Oct;30(10):2857-63. doi: 10.1002/1521-4141(200010)30:10<2857::AID-IMMU2857>3.0.CO;2-G.

Abstract

E2A, HEB and E2-2 genes encode a group of basic helix-loop-helix (bHLH) transcription factors that are structurally and functionally similar. Deletion of the genes encoding either of these proteins leads to early lethality and a block in B lymphocyte development. Evidence for a function in T lymphocyte development has, however, only been reported for E2A and HEB. To further elucidate the role of E2-2 at developmental stages that have proven difficult to study due to the early lethality phenotype of mice defective in E2-2, we generated and analyzed mice conditionally mutated in the E2-2 gene. These mice are mosaic with respect to E2-2 expression, consisting of cells with either one functional and one null mutated E2-2 allele or two null mutated alleles. Using this experimental model, we find that cells with a homozygous null mutated E2-2 gene are under-represented in B lymphocyte as well as T lymphocyte cell lineages as compared to other hematopoietic or non-hematopoietic cell lineages. Our data suggests that E2-2 deficiency leads to a partial block in both B and T lymphocyte development. The block in T cell development appears to occur at an early stage in differentiation, since skewing in the mosaicism is observed already in CD4+8+ double-positive thymocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocytes / pathology
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Differentiation
  • Cell Lineage
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Targeting
  • Genotype
  • Helix-Loop-Helix Motifs*
  • Hematopoiesis / genetics*
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Lymphocyte Count
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mosaicism
  • Nerve Tissue Proteins*
  • Spleen / pathology
  • T-Lymphocytes / pathology*
  • TCF Transcription Factors
  • Thymus Gland / pathology
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factor 4
  • Transcription Factors*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • TCF Transcription Factors
  • Tcf4 protein, mouse
  • Trans-Activators
  • Transcription Factor 4
  • Transcription Factors