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E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements
Ist Teil von
Cell, 1994-12, Vol.79 (5), p.885-892
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
1994
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression. We have now generated E2A (−/−) mice by gene targeting. E2A-null mutant mice fail to generate mature B cells. The arrest of B cell development occurs at an early stage, since no immunoglobulin DJ rearrangements can be detected in homozygous mutant mice. While immunoglobulin germline I
μ
RAG-1, mb-1, CD19, and λ5 transcripts are dramatically reduced in fetal livers of E2A (−/−) mice, B29 and μ° transcripts are present, but at lower levels. In addition, we show that
Pax-5 transcripts are significantly reduced in fetal livers of E2A (−/−) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation.