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) 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.
Bergqvist
I
I
Umeå Center for Molecular Medicine, Umeå University, Sweden.
Eriksson
M
M
Saarikettu
J
J
Eriksson
B
B
Corneliussen
B
B
Grundström
T
T
Holmberg
D
D
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D005838:Genotype; D018257:Helix-Loop-Helix Motifs; D006410:Hematopoiesis / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009030:Mosaicism; D009419:Nerve Tissue Proteins; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology*; D051820:TCF Transcription Factors; D013950:Thymus Gland / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000073940:Transcription Factor 4; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; D015534:Trans-Activators; D000073940:Transcription Factor 4; D014157:Transcription Factors