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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.

Type

Journal article

Journal

Cell

Publication Date

15/07/1994

Volume

78

Pages

45 - 57

Keywords

Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antibody Specificity, Base Sequence, Cell Line, Cell Nucleus, DNA-Binding Proteins, Embryonic and Fetal Development, Erythroid Precursor Cells, Erythropoiesis, Gene Expression, Genes, Lethal, Humans, LIM Domain Proteins, Liver, Metalloproteins, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Peptide Fragments, Phenotype, Proto-Oncogene Proteins, RNA, Messenger, Yolk Sac