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PMID: 14713950 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hematopoietic, angiogenic and eye defects in Meis1 mutant animals.

The EMBO journal ·Vol. 23 ·No. 2 ·2004-01-28 ·Pages 450-9

Hisa T, Spence SE, Rachel RA, Fujita M, Nakamura T, Ward JM, Devor-Henneman DE, Saiki Y, Kutsuna H, Tessarollo L, Jenkins NA, Copeland NG

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.

MeSH Terms
Animals Cell Transplantation Embryo, Mammalian/blood supply,cytology Erythroid Precursor Cells/cytology Eye Abnormalities/etiology Female Fetus/cytology Gene Targeting Germ-Line Mutation Hematopoiesis Hemorrhage/etiology Homeodomain Proteins/genetics,physiology Liver/cytology,embryology Megakaryocytes/cytology Mice Mice, Inbred C57BL Mice, Knockout Myeloid Ecotropic Viral Integration Site 1 Protein Myeloid Progenitor Cells/cytology Neoplasm Proteins/genetics,physiology Neovascularization, Pathologic/etiology
Chemicals
Homeodomain Proteins MEIS1 protein, human Meis1 protein, mouse Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hisa Tomoyuki
Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA.
Spence Sally E
Rachel Rivka A
Fujita Masami
Nakamura Takuro
Ward Jerrold M
Devor-Henneman Deborah E
Saiki Yuriko
Kutsuna Haruo
Tessarollo Lino
Jenkins Nancy A
Copeland Neal G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600038
Published
2004-01-28
Epub
2004-00-08
Pages
450-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1271748
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600038 PMC Full Text View journal details
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