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Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells

Brun, Ann LU ; Björnsson, Jon Mar LU ; Magnusson, Mattias LU ; Larsson, Nina LU ; Levéen, Per LU ; Ehinger, Mats LU ; Nilsson, Eva C LU and Karlsson, Stefan LU (2004) In Blood 103(11). p.4126-4133
Abstract
Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in adult BM and fetal liver, whereas lineage distribution was normal. Although the cell cycle kinetics of primitive progenitors was normal during endogenous... (More)
Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in adult BM and fetal liver, whereas lineage distribution was normal. Although the cell cycle kinetics of primitive progenitors was normal during endogenous hematopoiesis, defects in proliferative responses of BM Lin(-) Sca1(+) c-kit(+) stem and progenitor cells were observed in culture and in vivo after the transplantation of BM and fetal liver HSCs. Quantitative analysis of mRNA from fetal liver revealed that a deficiency of Hoxb4 alone changed the expression levels of several other Hox genes and of genes involved in cell cycle regulation. In summary, the deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs and impaired proliferative capacity. However, Hoxb4 is not required for the generation of HSCs or the maintenance of steady state hematopoiesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
103
issue
11
pages
4126 - 4133
publisher
American Society of Hematology
external identifiers
  • pmid:14962901
  • wos:000221657600028
  • scopus:2542467750
ISSN
1528-0020
DOI
10.1182/blood-2003-10-3557
language
English
LU publication?
yes
id
147015b9-6bb3-424c-8ff6-1df6c9956d40 (old id 1297750)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14962901&dopt=Abstract
date added to LUP
2009-07-13 14:54:51
date last changed
2017-07-30 03:50:08
@article{147015b9-6bb3-424c-8ff6-1df6c9956d40,
  abstract     = {Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in adult BM and fetal liver, whereas lineage distribution was normal. Although the cell cycle kinetics of primitive progenitors was normal during endogenous hematopoiesis, defects in proliferative responses of BM Lin(-) Sca1(+) c-kit(+) stem and progenitor cells were observed in culture and in vivo after the transplantation of BM and fetal liver HSCs. Quantitative analysis of mRNA from fetal liver revealed that a deficiency of Hoxb4 alone changed the expression levels of several other Hox genes and of genes involved in cell cycle regulation. In summary, the deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs and impaired proliferative capacity. However, Hoxb4 is not required for the generation of HSCs or the maintenance of steady state hematopoiesis.},
  author       = {Brun, Ann and Björnsson, Jon Mar and Magnusson, Mattias and Larsson, Nina and Levéen, Per and Ehinger, Mats and Nilsson, Eva C and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {11},
  pages        = {4126--4133},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells},
  url          = {http://dx.doi.org/10.1182/blood-2003-10-3557},
  volume       = {103},
  year         = {2004},
}