title: Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes.
abstract: 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.
authors: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Dawn E
authors: DE
authors: Watkins-Chow
authors: Joanna
authors: J
authors: Cooke
authors: Ruth
authors: R
authors: Pidsley
authors: Andrew
authors: A
authors: Edwards
authors: Rebecca
authors: R
authors: Slotkin
authors: Karen E
authors: KE
authors: Leeds
authors: Raymond
authors: R
authors: Mullen
authors: Laura L
authors: LL
authors: Baxter
authors: Thomas G
authors: TG
authors: Campbell
authors: Marion C
authors: MC
authors: Salzer
authors: Laura
authors: L
authors: Biondini
authors: Gretchen
authors: G
authors: Gibney
authors: Françoise
authors: F
authors: Phan Dinh Tuy
authors: Jamel
authors: J
authors: Chelly
authors: H Douglas
authors: HD
authors: Morris
authors: Johannes
authors: J
authors: Riegler
authors: Mark F
authors: MF
authors: Lythgoe
authors: Ruth M
authors: RM
authors: Arkell
authors: Fabrizio
authors: F
authors: Loreni
authors: Jonathan
authors: J
authors: Flint
authors: William J
authors: WJ
authors: Pavan
authors: David A
authors: DA
authors: Keays
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics / Q000473:pathology; D000818:Animals; D049628:Body Size / Q000235:genetics; D002490:Central Nervous System / Q000254:growth & development / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics* / Q000502:physiology; D012270:Ribosomes / Q000235:genetics
chemical_list: D012269:Ribosomal Proteins; C037442:ribosomal protein S7
references: Pigment Cell Melanoma Res. 2010 Dec;23(6):781-94
references: 20849464
references: J Cell Biol. 2010 Sep 6;190(5):853-66
references: 20819938
references: Mol Cell. 2009 Apr 10;34(1):3-11
references: 19362532
references: RNA. 2008 Sep;14(9):1918-29
references: 18697920
references: Int J Biochem Cell Biol. 2011 Aug;43(8):1218-27
references: 21550419
references: Hum Mol Genet. 2008 Jul 15;17(14):2118-31
references: 18397875
references: Stem Cells. 2006 Sep;24(9):2034-44
references: 16741228
references: Am J Hum Genet. 2010 Feb 12;86(2):222-8
references: 20116044
references: Nat Protoc. 2009;4(7):1073-81
references: 19561590
references: Science. 2011 Dec 16;334(6062):1524-9
references: 22096102
references: Haematologica. 2008 Nov;93(11):1601-4
references: 18978295
references: Eukaryot Cell. 2004 Dec;3(6):1619-26
references: 15590835
references: PLoS One. 2009;4(1):e4152
references: 19129914
references: Nat Genet. 1999 Feb;21(2):169-75
references: 9988267
references: PLoS Biol. 2010 Oct 26;8(10):e1000522
references: 21048991
references: Nat Rev Mol Cell Biol. 2007 Jul;8(7):574-85
references: 17519961
references: Hum Mutat. 2012 Jul;33(7):1037-44
references: 22431104
references: Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12477-82
references: 16109771
references: Genes Dev. 2005 Dec 15;19(24):3070-82
references: 16357222
references: Blood. 2001 Dec 1;98(12):3261-73
references: 11719363
references: Immunity. 2007 Jun;26(6):759-72
references: 17555992
references: Genes Dev. 2012 May 15;26(10):1028-40
references: 22588717
references: Br J Haematol. 2011 Mar;152(5):648-54
references: 21223253
references: J Pathol. 2011 Aug;224(4):540-52
references: 21674502
references: Blood Cells Mol Dis. 2006 Mar-Apr;36(2):259-64
references: 16458028
references: Methods Enzymol. 1993;225:361-73
references: 8231863
references: J Hered. 1950 Aug;41(8):208-15
references: 14779008
references: Genome Biol. 2007;8(10):R216
references: 17927810
references: Cell Biol Int. 2011 May;35(5):449-52
references: 21114473
references: Am J Hum Genet. 2006 Dec;79(6):1110-8
references: 17186470
references: Nat Genet. 2008 Aug;40(8):963-70
references: 18641651
references: Genetics. 2012 May;191(1):107-18
references: 22377630
references: J Immunol. 2011 Jul 15;187(2):664-75
references: 21690328
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W645-50
references: 16912992
references: Nat Genet. 2000 Aug;25(4):440-3
references: 10932191
references: Hum Mutat. 2007 Dec;28(12):1178-82
references: 17647292
references: Am J Hum Genet. 2008 Dec;83(6):769-80
references: 19061985
references: Development. 2004 Aug;131(16):3907-20
references: 15289434
references: Mol Cell Biol. 2009 May;29(10):2489-504
references: 19273598
references: Blood. 2003 Dec 1;102(12):3938-46
references: 12907435
references: Science. 2011 Feb 11;331(6018):730-6
references: 21205638
references: Dev Biol. 2001 Sep 15;237(2):245-57
references: 11543611
references: Mol Cell Biol. 2004 May;24(9):4032-7
references: 15082795
references: Magn Reson Med. 1986 Dec;3(6):823-33
references: 3821461
references: Genesis. 2004 Oct;40(2):109-117
references: 15384171
references: Dev Neurosci. 2008;30(1-3):171-86
references: 18075264
references: J Biol Chem. 1992 Feb 15;267(5):3008-13
references: 1737755
references: PLoS One. 2006 Dec 20;1:e37
references: 17183665
references: Differentiation. 2000 Oct;66(2-3):81-92
references: 11100899
references: Hum Mol Genet. 2007 Jul 15;16(14):1720-7
references: 17517689
references: Mol Cell. 2005 Oct 28;20(2):263-75
references: 16246728
references: Neuroscience. 2010 Dec 29;171(4):1131-40
references: 20933575
references: Genomics. 2001 Mar 15;72(3):223-30
references: 11401437
references: Nat Protoc. 2006;1(1):7-12
references: 17406205
references: Cell. 2011 Apr 29;145(3):383-397
references: 21529712
references: Bioinformatics. 2001 Dec;17(12):1152-7
references: 11751223
references: Blood. 2008 Sep 1;112(5):1582-92
references: 18535205
references: Mol Cell. 2007 Jan 12;25(1):113-26
references: 17218275
references: Nucleic Acids Res. 1981 Oct 10;9(19):4951-66
references: 7312622
references: Br J Haematol. 2008 Sep;142(6):859-76
references: 18671700
references: Lancet. 2003 Aug 23;362(9384):651-62
references: 12944067
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W321-6
references: 15215403