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Verhagen-Oldenampsen JH, Haanstra JR, van Strien PM, et al. Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors. Anemia. 2012;2012:783068doi: 10.1155/2012/783068.
Verhagen-Oldenampsen, J. H., Haanstra, J. R., van Strien, P. M., Valkhof, M., Touw, I. P., & von Lindern, M. (2012). Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors. Anemia, 2012783068. https://doi.org/10.1155/2012/783068
Verhagen-Oldenampsen, Judith H E, et al. "Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors." Anemia vol. 2012 (2012): 783068. doi: https://doi.org/10.1155/2012/783068
Verhagen-Oldenampsen JH, Haanstra JR, van Strien PM, Valkhof M, Touw IP, von Lindern M. Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors. Anemia. 2012;2012:783068. doi: 10.1155/2012/783068. Epub 2012 Jun 03. PMID: 22701168; PMCID: PMC3371671.
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Anemia. 2012;2012:783068. doi: 10.1155/2012/783068. Epub 2012 Jun 03.

Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors.

Anemia

Judith H E Verhagen-Oldenampsen, Jurgen R Haanstra, Paulina M H van Strien, Marijke Valkhof, Ivo P Touw, Marieke von Lindern

Affiliations

  1. Department of Hematology, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.

PMID: 22701168 PMCID: PMC3371671 DOI: 10.1155/2012/783068

Abstract

The endonuclease complex Ercc1/Xpf is involved in interstrand crosslink repair and functions downstream of the Fanconi pathway. Loss of Ercc1 causes hematopoietic defects similar to those seen in Fanconi Anemia. Ercc1(-/-) mice die 3-4 weeks after birth, which prevents long-term follow up of the hematopoietic compartment. We used alternative Ercc1 mouse models to examine the effect of low or absent Ercc1 activity on hematopoiesis. Tie2-Cre-driven deletion of a floxed Ercc1 allele was efficient (>80%) in fetal liver hematopoietic cells. Hematopoietic stem and progenitor cells (HSPCs) with a deleted allele were maintained in mice up to 1 year of age when harboring a wt allele, but were progressively outcompeted when the deleted allele was combined with a knockout allele. Mice with a minimal Ercc1 activity expressed by 1 or 2 hypomorphic Ercc1 alleles have an extended life expectancy, which allows analysis of HSPCs at 10 and 20 weeks of age. The HSPC compartment was affected in all Ercc1-deficient models. Actively proliferating multipotent progenitors were most affected as were myeloid and erythroid clonogenic progenitors. In conclusion, lack of Ercc1 results in a severe competitive disadvantage of HSPCs and is most deleterious in proliferating progenitor cells.

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