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

E2A, HEB and E2-2 genes encode a group of basic helix-loop-helix (bHLH) tra nscription 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 lymphocy te development has, however, only been reported for E2A and HEB. To further elucidate the role of E2-2 at developmental stages that have proven diffic ult 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. Th ese mice are mosaic with respect to E2-2 expression, consisting of cells wi th either one functional and one null mutated E2-2 allele or two null mutat ed alleles. Using this experimental model, we find that cells with a homozy gous null mutated E2-2 gene are under-represented in B lymphocyte as well a s T lymphocyte cell lineages as compared to other hematopoietic or non-hema topoietic 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 d evelopment appears to occur at an early stage in differentiation, since ske wing in the mosaicism is observed already in CD4(+)8(+) double-positive thy mocytes.