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

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.