Abstract
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 mu RAG-1, mb-1, CD19, and lambda 5 transcripts are dramatically reduced in fetal livers of E2A (-/-) mice, B29 and mu degrees 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / physiology*
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Base Sequence
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Cell Differentiation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Rearrangement
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Genes, Immunoglobulin / genetics*
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Homeodomain Proteins*
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Homozygote
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Immunoglobulin lambda-Chains / genetics
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Lymphoid Tissue / immunology
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Mice
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Mice, Mutant Strains
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Molecular Sequence Data
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Proteins / genetics
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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Immunoglobulin lambda-Chains
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Proteins
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RNA, Messenger
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TCF Transcription Factors
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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RAG-1 protein