1. The Oncogenic Cysteine-rich LIM domain protein Rbtn2 is essential for erythroid development
- Author
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Mark B. L. Carlton, Alan J. Warren, William H. Colledge, Andrew J.H. Smith, Terence H. Rabbitts, and Martin J. Evans
- Subjects
LMO2 ,Molecular Sequence Data ,Mutant ,Gene Expression ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Embryonic and Fetal Development ,Mice ,Antibody Specificity ,Proto-Oncogene Proteins ,Metalloproteins ,medicine ,Animals ,Humans ,Erythropoiesis ,Amino Acid Sequence ,RNA, Messenger ,Nuclear protein ,Yolk sac ,Adaptor Proteins, Signal Transducing ,Yolk Sac ,LIM domain ,Cell Nucleus ,Erythroid Precursor Cells ,Base Sequence ,LIM Domain Proteins ,Molecular biology ,Null allele ,Peptide Fragments ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Phenotype ,medicine.anatomical_structure ,Liver ,Mutation ,embryonic structures ,Genes, Lethal ,TAL1 - Abstract
The LIM domain protein rbtn2 is associated with T cell acute leukemias. We demonstrate that rbtn2 is a nuclear protein expressed in the erythroid lineage in vivo, and using homologous recombination, we show that it is essential for erythroid development in mice. The homozygous rbtn2 null mutation leads to failure of yolk sac erythropoiesis and embryonic lethality around E10.5. Moreover, in vitro differentiation of yolk sac tissue from homozygous mutant mice and sequentially targeted double-mutant ES cells demonstrates a block to erythroid development. This shows a pivotal role for a LIM domain protein in lineage specification during mammalian development and suggests that RBTN2 and GATA-1 are critical at similar stages of erythroid differentiation.
- Published
- 1994
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