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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| Materialtyp: | Artikel |
| Språk: | en_US |
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eLife Sciences Publications, Ltd.
2014
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| Länkar: | http://hdl.handle.net/1721.1/87015 |
| _version_ | 1826194227382452224 |
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| author | Goff, Loyal Kellis, Manolis Sauvageau, Martin Lodato, Simona Bonev, Boyan Groff, Abigail F. Gerhardinger, Chiara Sanchez-Gomez, Diana B. Hacisuleyman, Ezgi Li, Eric Spence, Matthew Liapis, Stephen C. Mallard, William Morse, Michael Swerdel, Mavis R. D'Ecclessis, Michael F. Moore, Jennifer C. Lai, Venus Gong, Guochun Yancopoulos, George D. Frendewey, David Hart, Ronald P. Valenzuela, David M. Arlotta, Paola Rinn, John L. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Goff, Loyal Kellis, Manolis Sauvageau, Martin Lodato, Simona Bonev, Boyan Groff, Abigail F. Gerhardinger, Chiara Sanchez-Gomez, Diana B. Hacisuleyman, Ezgi Li, Eric Spence, Matthew Liapis, Stephen C. Mallard, William Morse, Michael Swerdel, Mavis R. D'Ecclessis, Michael F. Moore, Jennifer C. Lai, Venus Gong, Guochun Yancopoulos, George D. Frendewey, David Hart, Ronald P. Valenzuela, David M. Arlotta, Paola Rinn, John L. |
| author_sort | Goff, Loyal |
| collection | MIT |
| 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[superscript −/−] neonates, whereas linc–Brn1b[superscript −/−] 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. |
| first_indexed | 2024-09-23T09:52:52Z |
| format | Article |
| id | mit-1721.1/87015 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:52:52Z |
| publishDate | 2014 |
| publisher | eLife Sciences Publications, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/870152022-09-26T14:16:08Z Multiple knockout mouse models reveal lincRNAs are required for life and brain development Goff, Loyal Kellis, Manolis Sauvageau, Martin Lodato, Simona Bonev, Boyan Groff, Abigail F. Gerhardinger, Chiara Sanchez-Gomez, Diana B. Hacisuleyman, Ezgi Li, Eric Spence, Matthew Liapis, Stephen C. Mallard, William Morse, Michael Swerdel, Mavis R. D'Ecclessis, Michael F. Moore, Jennifer C. Lai, Venus Gong, Guochun Yancopoulos, George D. Frendewey, David Hart, Ronald P. Valenzuela, David M. Arlotta, Paola Rinn, John L. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Goff, Loyal Kellis, Manolis 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[superscript −/−] neonates, whereas linc–Brn1b[superscript −/−] 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. National Science Foundation (U.S.) (Postdoctoral Fellowship in Biology) 2014-05-15T19:25:46Z 2014-05-15T19:25:46Z 2013-12 2013-10 Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/87015 Sauvageau, M., L. A. Goff, S. Lodato, B. Bonev, A. F. Groff, C. Gerhardinger, D. B. Sanchez-Gomez, et al. “Multiple Knockout Mouse Models Reveal lincRNAs Are Required for Life and Brain Development.” eLife 2, no. 0 (December 31, 2013): e01749–e01749. en_US http://dx.doi.org/10.7554/eLife.01749 eLife Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf eLife Sciences Publications, Ltd. Elife |
| spellingShingle | Goff, Loyal Kellis, Manolis Sauvageau, Martin Lodato, Simona Bonev, Boyan Groff, Abigail F. Gerhardinger, Chiara Sanchez-Gomez, Diana B. Hacisuleyman, Ezgi Li, Eric Spence, Matthew Liapis, Stephen C. Mallard, William Morse, Michael Swerdel, Mavis R. D'Ecclessis, Michael F. Moore, Jennifer C. Lai, Venus Gong, Guochun Yancopoulos, George D. Frendewey, David Hart, Ronald P. Valenzuela, David M. Arlotta, Paola Rinn, John L. Multiple knockout mouse models reveal lincRNAs are required for life and brain development |
| title | 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_short | 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 |
| url | http://hdl.handle.net/1721.1/87015 |
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