Hematopoietic, angiogenic and eye defects in Meis1 mutant animals
Open Access
- 8 January 2004
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 23 (2), 450-459
- https://doi.org/10.1038/sj.emboj.7600038
Abstract
Meis1 and Hoxa9 expression is upregulated by retroviral integration in murine myeloid leukemias and in human leukemias carrying MLL translocations. Both genes also cooperate to induce leukemia in a mouse leukemia acceleration assay, which can be explained, in part, by their physical interaction with each other as well as the PBX family of homeodomain proteins. Here we show that Meis1 ‐deficient embryos have partially duplicated retinas and smaller lenses than normal. They also fail to produce megakaryocytes, display extensive hemorrhaging, and die by embryonic day 14.5. In addition, Meis1 ‐deficient embryos lack well‐formed capillaries, although larger blood vessels are normal. Definitive myeloerythroid lineages are present in the mutant embryos, but the total numbers of colony‐forming cells are dramatically reduced. Mutant fetal liver cells also fail to radioprotect lethally irradiated animals and they compete poorly in repopulation assays even though they can repopulate all hematopoietic lineages. These and other studies showing that Meis1 is expressed at high levels in hematopoietic stem cells (HSCs) suggest that Meis1 may also be required for the proliferation/self‐renewal of the HSC.Keywords
This publication has 56 references indexed in Scilit:
- Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 geneBlood, 2003
- A Conformational Change in PBX1A Is Necessary for Its Nuclear LocalizationExperimental Cell Research, 2000
- Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1bThe EMBO Journal, 1998
- Biology of thrombopoietinCurrent Opinion in Pediatrics, 1998
- The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP96 and class I homeoprotein HOXA9Nature Genetics, 1996
- Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemiaNature Genetics, 1996
- AML1, the Target of Multiple Chromosomal Translocations in Human Leukemia, Is Essential for Normal Fetal Liver HematopoiesisCell, 1996
- Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesisNature Genetics, 1995
- Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formationNature, 1995
- Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice.Genes & Development, 1991