The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development.
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.
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
A J
AJ
Warren
W H
WH
Colledge
M B
MB
Carlton
M J
MJ
Evans
A J
AJ
Smith
T H
TH
Rabbitts
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D005314:Embryonic and Fetal Development; D015672:Erythroid Precursor Cells / Q000737:chemistry / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D015870:Gene Expression; D005804:Genes, Lethal / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D008099:Liver / Q000737:chemistry; D008667:Metalloproteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D015017:Yolk Sac / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger