A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.
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 complexit...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2010
|
| _version_ | 1797098785089781760 |
|---|---|
| author | Barlow, J Drynan, L Hewett, DR Holmes, L Lorenzo-Abalde, S Lane, A Jolin, H Pannell, R Middleton, A Wong, S Warren, A Wainscoat, J Boultwood, J McKenzie, A |
| author_facet | Barlow, J Drynan, L Hewett, DR Holmes, L Lorenzo-Abalde, S Lane, A Jolin, H Pannell, R Middleton, A Wong, S Warren, A Wainscoat, J Boultwood, J McKenzie, A |
| author_sort | Barlow, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:14:37Z |
| format | Journal article |
| id | oxford-uuid:dcc18571-48a2-46cc-aed2-61da643457b6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:14:37Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:dcc18571-48a2-46cc-aed2-61da643457b62022-03-27T09:19:51ZA p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dcc18571-48a2-46cc-aed2-61da643457b6EnglishSymplectic Elements at Oxford2010Barlow, JDrynan, LHewett, DRHolmes, LLorenzo-Abalde, SLane, AJolin, HPannell, RMiddleton, AWong, SWarren, AWainscoat, JBoultwood, JMcKenzie, AThe 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. |
| spellingShingle | Barlow, J Drynan, L Hewett, DR Holmes, L Lorenzo-Abalde, S Lane, A Jolin, H Pannell, R Middleton, A Wong, S Warren, A Wainscoat, J Boultwood, J McKenzie, A A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title_full | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title_fullStr | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title_full_unstemmed | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title_short | A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. |
| title_sort | p53 dependent mechanism underlies macrocytic anemia in a mouse model of human 5q syndrome |
| work_keys_str_mv | AT barlowj ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT drynanl ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT hewettdr ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT holmesl ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT lorenzoabaldes ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT lanea ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT jolinh ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT pannellr ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT middletona ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT wongs ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT warrena ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT wainscoatj ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT boultwoodj ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT mckenziea ap53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT barlowj p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT drynanl p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT hewettdr p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT holmesl p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT lorenzoabaldes p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT lanea p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT jolinh p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT pannellr p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT middletona p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT wongs p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT warrena p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT wainscoatj p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT boultwoodj p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome AT mckenziea p53dependentmechanismunderliesmacrocyticanemiainamousemodelofhuman5qsyndrome |