title: E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements.
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.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla 92130.
authors.forename: G
authors.initials: G
authors.lastname: Bain
authors.forename: E C
authors.initials: EC
authors.lastname: Maandag
authors.forename: D J
authors.initials: DJ
authors.lastname: Izon
authors.forename: D
authors.initials: D
authors.lastname: Amsen
authors.forename: A M
authors.initials: AM
authors.lastname: Kruisbeek
authors.forename: B C
authors.initials: BC
authors.lastname: Weintraub
authors.forename: I
authors.initials: I
authors.lastname: Krop
authors.forename: M S
authors.initials: MS
authors.lastname: Schlissel
authors.forename: A J
authors.initials: AJ
authors.lastname: Feeney
authors.forename: M
authors.initials: M
authors.lastname: van Roon
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics*; D018398:Homeodomain Proteins; D006720:Homozygote; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007146:Immunoglobulin lambda-Chains; D011506:Proteins; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C064658:RAG-1 protein