Multiple knockout mouse models reveal lincRNAs are required for life and brain development
Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRN...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01749 |
| id |
doaj-5fdb35f4c02f45c69bc508db25a26cb3 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Martin Sauvageau Loyal A Goff Simona Lodato Boyan Bonev Abigail F Groff Chiara Gerhardinger Diana B Sanchez-Gomez Ezgi Hacisuleyman Eric Li Matthew Spence Stephen C Liapis William Mallard Michael Morse Mavis R Swerdel Michael F D’Ecclessis Jennifer C Moore Venus Lai Guochun Gong George D Yancopoulos David Frendewey Manolis Kellis Ronald P Hart David M Valenzuela Paola Arlotta John L Rinn |
| spellingShingle |
Martin Sauvageau Loyal A Goff Simona Lodato Boyan Bonev Abigail F Groff Chiara Gerhardinger Diana B Sanchez-Gomez Ezgi Hacisuleyman Eric Li Matthew Spence Stephen C Liapis William Mallard Michael Morse Mavis R Swerdel Michael F D’Ecclessis Jennifer C Moore Venus Lai Guochun Gong George D Yancopoulos David Frendewey Manolis Kellis Ronald P Hart David M Valenzuela Paola Arlotta John L Rinn Multiple knockout mouse models reveal lincRNAs are required for life and brain development eLife long noncoding RNA knockout mouse model lethality developmental defect brain development |
| author_facet |
Martin Sauvageau Loyal A Goff Simona Lodato Boyan Bonev Abigail F Groff Chiara Gerhardinger Diana B Sanchez-Gomez Ezgi Hacisuleyman Eric Li Matthew Spence Stephen C Liapis William Mallard Michael Morse Mavis R Swerdel Michael F D’Ecclessis Jennifer C Moore Venus Lai Guochun Gong George D Yancopoulos David Frendewey Manolis Kellis Ronald P Hart David M Valenzuela Paola Arlotta John L Rinn |
| author_sort |
Martin Sauvageau |
| title |
Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title_short |
Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title_full |
Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title_fullStr |
Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title_full_unstemmed |
Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title_sort |
multiple knockout mouse models reveal lincrnas are required for life and brain development |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2013-12-01 |
| description |
Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc–Brn1b and linc–Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr−/− neonates, whereas linc–Brn1b−/− mutants displayed distinct abnormalities in the generation of upper layer II–IV neurons in the neocortex. This study demonstrates that lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules. |
| topic |
long noncoding RNA knockout mouse model lethality developmental defect brain development |
| url |
https://elifesciences.org/articles/01749 |
| work_keys_str_mv |
AT martinsauvageau multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT loyalagoff multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT simonalodato multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT boyanbonev multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT abigailfgroff multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT chiaragerhardinger multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT dianabsanchezgomez multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT ezgihacisuleyman multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT ericli multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT matthewspence multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT stephencliapis multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT williammallard multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT michaelmorse multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT mavisrswerdel multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT michaelfdecclessis multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT jennifercmoore multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT venuslai multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT guochungong multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT georgedyancopoulos multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT davidfrendewey multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT manoliskellis multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT ronaldphart multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT davidmvalenzuela multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT paolaarlotta multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment AT johnlrinn multipleknockoutmousemodelsreveallincrnasarerequiredforlifeandbraindevelopment |
| _version_ |
1721477206872424448 |
| spelling |
doaj-5fdb35f4c02f45c69bc508db25a26cb32021-05-04T22:53:09ZengeLife Sciences Publications LtdeLife2050-084X2013-12-01210.7554/eLife.01749Multiple knockout mouse models reveal lincRNAs are required for life and brain developmentMartin Sauvageau0Loyal A Goff1Simona Lodato2Boyan Bonev3Abigail F Groff4Chiara Gerhardinger5Diana B Sanchez-Gomez6Ezgi Hacisuleyman7Eric Li8Matthew Spence9Stephen C Liapis10William Mallard11Michael Morse12Mavis R Swerdel13Michael F D’Ecclessis14Jennifer C Moore15Venus Lai16Guochun Gong17George D Yancopoulos18David Frendewey19Manolis Kellis20Ronald P Hart21David M Valenzuela22Paola Arlotta23John L Rinn24Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, United StatesDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, United StatesDepartment of Genetics, Rutgers, The State University of New Jersey, New Brunswick, United StatesRegeneron Pharmaceuticals Inc., Tarrytown, United StatesRegeneron Pharmaceuticals Inc., Tarrytown, United StatesRegeneron Pharmaceuticals Inc., Tarrytown, United StatesRegeneron Pharmaceuticals Inc., Tarrytown, United StatesBroad Institute of MIT and Harvard, Cambridge, United States; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, United StatesRegeneron Pharmaceuticals Inc., Tarrytown, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United StatesMany studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc–Brn1b and linc–Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr−/− neonates, whereas linc–Brn1b−/− mutants displayed distinct abnormalities in the generation of upper layer II–IV neurons in the neocortex. This study demonstrates that lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules.https://elifesciences.org/articles/01749long noncoding RNAknockout mouse modellethalitydevelopmental defectbrain development |