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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3561062?pdf=render |
| _version_ | 1818136634259931136 |
|---|---|
| author | Dawn E Watkins-Chow Joanna Cooke Ruth Pidsley Andrew Edwards Rebecca Slotkin Karen E Leeds Raymond Mullen Laura L Baxter Thomas G Campbell Marion C Salzer Laura Biondini Gretchen Gibney Françoise Phan Dinh Tuy Jamel Chelly H Douglas Morris Johannes Riegler Mark F Lythgoe Ruth M Arkell Fabrizio Loreni Jonathan Flint William J Pavan David A Keays |
| author_facet | Dawn E Watkins-Chow Joanna Cooke Ruth Pidsley Andrew Edwards Rebecca Slotkin Karen E Leeds Raymond Mullen Laura L Baxter Thomas G Campbell Marion C Salzer Laura Biondini Gretchen Gibney Françoise Phan Dinh Tuy Jamel Chelly H Douglas Morris Johannes Riegler Mark F Lythgoe Ruth M Arkell Fabrizio Loreni Jonathan Flint William J Pavan David A Keays |
| author_sort | Dawn E Watkins-Chow |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T09:43:31Z |
| format | Article |
| id | doaj.art-8fe6fb4f16a946d0a4157894bf410bd8 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T09:43:31Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-8fe6fb4f16a946d0a4157894bf410bd82022-12-22T01:12:37ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0191e100309410.1371/journal.pgen.1003094Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes.Dawn E Watkins-ChowJoanna CookeRuth PidsleyAndrew EdwardsRebecca SlotkinKaren E LeedsRaymond MullenLaura L BaxterThomas G CampbellMarion C SalzerLaura BiondiniGretchen GibneyFrançoise Phan Dinh TuyJamel ChellyH Douglas MorrisJohannes RieglerMark F LythgoeRuth M ArkellFabrizio LoreniJonathan FlintWilliam J PavanDavid A KeaysThe 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.http://europepmc.org/articles/PMC3561062?pdf=render |
| spellingShingle | Dawn E Watkins-Chow Joanna Cooke Ruth Pidsley Andrew Edwards Rebecca Slotkin Karen E Leeds Raymond Mullen Laura L Baxter Thomas G Campbell Marion C Salzer Laura Biondini Gretchen Gibney Françoise Phan Dinh Tuy Jamel Chelly H Douglas Morris Johannes Riegler Mark F Lythgoe Ruth M Arkell Fabrizio Loreni Jonathan Flint William J Pavan David A Keays Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes. PLoS Genetics |
| 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 |
| url | http://europepmc.org/articles/PMC3561062?pdf=render |
| work_keys_str_mv | AT dawnewatkinschow mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT joannacooke mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT ruthpidsley mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT andrewedwards mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT rebeccaslotkin mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT kareneleeds mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT raymondmullen mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT lauralbaxter mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT thomasgcampbell mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT marioncsalzer mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT laurabiondini mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT gretchengibney mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT francoisephandinhtuy mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT jamelchelly mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT hdouglasmorris mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT johannesriegler mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT markflythgoe mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT ruthmarkell mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT fabrizioloreni mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT jonathanflint mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT williamjpavan mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes AT davidakeays mutationofthediamondblackfananemiagenerps7inmouseresultsinmorphologicalandneuroanatomicalphenotypes |