E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements.
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.
Bain
G
G
Department of Biology, University of California, San Diego, La Jolla 92130.
Maandag
E C
EC
Izon
D J
DJ
Amsen
D
D
Kruisbeek
A M
AM
Weintraub
B C
BC
Krop
I
I
Schlissel
M S
MS
Feeney
A J
AJ
van Roon
M
M
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*
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