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Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that enco...

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Autores principales: Watkins-Chow, Dawn E., Cooke, Joanna, Pidsley, Ruth, Edwards, Andrew, Slotkin, Rebecca, Leeds, Karen E., Mullen, Raymond, Baxter, Laura L., Campbell, Thomas G., Salzer, Marion C., Biondini, Laura, Gibney, Gretchen, Phan Dinh Tuy, Françoise, Chelly, Jamel, Morris, H. Douglas, Riegler, Johannes, Lythgoe, Mark F., Arkell, Ruth M., Loreni, Fabrizio, Flint, Jonathan, Pavan, William J., Keays, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561062/
https://www.ncbi.nlm.nih.gov/pubmed/23382688
http://dx.doi.org/10.1371/journal.pgen.1003094
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author Watkins-Chow, Dawn E.
Cooke, Joanna
Pidsley, Ruth
Edwards, Andrew
Slotkin, Rebecca
Leeds, Karen E.
Mullen, Raymond
Baxter, Laura L.
Campbell, Thomas G.
Salzer, Marion C.
Biondini, Laura
Gibney, Gretchen
Phan Dinh Tuy, Françoise
Chelly, Jamel
Morris, H. Douglas
Riegler, Johannes
Lythgoe, Mark F.
Arkell, Ruth M.
Loreni, Fabrizio
Flint, Jonathan
Pavan, William J.
Keays, David A.
author_facet Watkins-Chow, Dawn E.
Cooke, Joanna
Pidsley, Ruth
Edwards, Andrew
Slotkin, Rebecca
Leeds, Karen E.
Mullen, Raymond
Baxter, Laura L.
Campbell, Thomas G.
Salzer, Marion C.
Biondini, Laura
Gibney, Gretchen
Phan Dinh Tuy, Françoise
Chelly, Jamel
Morris, H. Douglas
Riegler, Johannes
Lythgoe, Mark F.
Arkell, Ruth M.
Loreni, Fabrizio
Flint, Jonathan
Pavan, William J.
Keays, David A.
author_sort Watkins-Chow, Dawn E.
collection PubMed
description The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7(Mtu) and Rps7(Zma)) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes.
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spelling pubmed-35610622013-02-04 Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes Watkins-Chow, Dawn E. Cooke, Joanna Pidsley, Ruth Edwards, Andrew Slotkin, Rebecca Leeds, Karen E. Mullen, Raymond Baxter, Laura L. Campbell, Thomas G. Salzer, Marion C. Biondini, Laura Gibney, Gretchen Phan Dinh Tuy, Françoise Chelly, Jamel Morris, H. Douglas Riegler, Johannes Lythgoe, Mark F. Arkell, Ruth M. Loreni, Fabrizio Flint, Jonathan Pavan, William J. Keays, David A. PLoS Genet Research Article The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7(Mtu) and Rps7(Zma)) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes. Public Library of Science 2013-01-31 /pmc/articles/PMC3561062/ /pubmed/23382688 http://dx.doi.org/10.1371/journal.pgen.1003094 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Watkins-Chow, Dawn E.
Cooke, Joanna
Pidsley, Ruth
Edwards, Andrew
Slotkin, Rebecca
Leeds, Karen E.
Mullen, Raymond
Baxter, Laura L.
Campbell, Thomas G.
Salzer, Marion C.
Biondini, Laura
Gibney, Gretchen
Phan Dinh Tuy, Françoise
Chelly, Jamel
Morris, H. Douglas
Riegler, Johannes
Lythgoe, Mark F.
Arkell, Ruth M.
Loreni, Fabrizio
Flint, Jonathan
Pavan, William J.
Keays, David A.
Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title_full Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title_fullStr Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title_full_unstemmed Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title_short Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes
title_sort mutation of the diamond-blackfan anemia gene rps7 in mouse results in morphological and neuroanatomical phenotypes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561062/
https://www.ncbi.nlm.nih.gov/pubmed/23382688
http://dx.doi.org/10.1371/journal.pgen.1003094
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