2026-06-14T03:40:23Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/102902024-11-29T14:12:55Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Varetti, Gianluca
author
Gómez-López, Gonzalo
author
Martinez, Dolores
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Comunidad de Madrid (España)
funder
Botín Foundation
funder
Fundación Ramón Areces
funder
Fundación AXA
funder
Centro Nacional de Investigaciones Oncológicas Carlos III (España)
2020-06-08T16:34:16Z
2020-06-08T16:34:16Z
2015-10-27
Cell Press
10.1016/j.celrep.2015.09.038
2211-1247
Cell reports
26489471
http://hdl.handle.net/20.500.12105/10290
Diamond-Blackfan anemia (DBA) is characterized by anemia and cancer susceptibility and is caused by mutations in ribosomal genes, including RPL11. Here, we report that Rpl11-heterozygous mouse embryos are not viable and that Rpl11 homozygous deletion in adult mice results in death within a few weeks, accompanied by bone marrow aplasia and intestinal atrophy. Importantly, Rpl11 heterozygous deletion in adult mice results in anemia associated with decreased erythroid progenitors and defective erythroid maturation. These defects are also present in mice transplanted with inducible heterozygous Rpl11 bone marrow and, therefore, are intrinsic to the hematopoietic system. Additionally, heterozygous Rpl11 mice present increased susceptibility to radiation-induced lymphomagenesis. In this regard, total or partial deletion of Rpl11 compromises p53 activation upon ribosomal stress or DNA damage in fibroblasts. Moreover, fibroblasts and hematopoietic tissues from heterozygous Rpl11 mice present higher basal cMYC levels. We conclude that Rpl11-deficient mice recapitulate DBA disorder, including cancer predisposition.
eng
EXPRESSION
MUTATIONS
RIBOSOMAL-PROTEIN L11
C-MYC
P53 ACTIVATION
ERYTHROID-DIFFERENTIATION
Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis.
journal article
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