Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/85990
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome |
Author: | Barlow, J. Drynan, L. Hewett, D. Holmes, L. Lorenzo-Abalde, S. Lane, A. Jolin, H. Pannell, R. Middleton, A. Wong, S. Warren, A. Wainscoat, J. Boultwood, J. McKenzie, A. |
Citation: | Nature Medicine, 2010; 16(1):59-66 |
Publisher: | Nature Publishing Group |
Issue Date: | 2010 |
ISSN: | 1078-8956 1546-170X |
Statement of Responsibility: | Jillian L Barlow, Lesley F Drynan, Duncan R Hewett, Luke R Holmes, Silvia Lorenzo-Abalde, Alison L Lane, Helen E Jolin, Richard Pannell, Angela J Middleton, See Heng Wong, Alan J Warren, James S Wainscoat, Jacqueline Boultwood & Andrew N J McKenzie |
Abstract: | The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q– syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74–Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q– syndrome. |
Keywords: | Hematopoietic Stem Cells Chromosomes, Mammalian Animals Humans Mice Anemia, Macrocytic Myelodysplastic Syndromes Disease Models, Animal Chromosome Deletion Apoptosis Synteny Genes, p53 |
Rights: | © 2010 Nature America, Inc. |
DOI: | 10.1038/nm.2063 |
Published version: | http://dx.doi.org/10.1038/nm.2063 |
Appears in Collections: | Aurora harvest 2 Genetics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.