| First Author | Verhagen-Oldenampsen JH | Year | 2012 |
| Journal | Anemia | Volume | 2012 |
| Pages | 783068 | PubMed ID | 22701168 |
| Mgi Jnum | J:206925 | Mgi Id | MGI:5553268 |
| Doi | 10.1155/2012/783068 | Citation | Verhagen-Oldenampsen JH, et al. (2012) Loss of ercc1 results in a time- and dose-dependent reduction of proliferating early hematopoietic progenitors. Anemia 2012:783068 |
| abstractText | 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. |
