Deletion of Ultraconserved Elements Yields Viable Mice

@article{citeulike:1622056, abstract = {Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.}, author = {Ahituv, Nadav and Zhu, Yiwen and Visel, Axel and Holt, Amy and Afzal, Veena and Pennacchio, Len A. and Rubin, Edward M. }, citeulike-article-id = {1622056}, doi = {http://dx.doi.org/10.1371/journal.pbio.0050234}, journal = {PLoS Biology}, keywords = {conservation, development, expression, rodents}, month = {September}, number = {9}, pages = {e234+}, posted-at = {2007-09-05 17:57:49}, priority = {3}, title = {Deletion of Ultraconserved Elements Yields Viable Mice}, url = {http://dx.doi.org/10.1371/journal.pbio.0050234}, volume = {5}, year = {2007} }

TY - JOUR ID - citeulike:1622056 L3 - citeulike-article-id:1622056 TI - Deletion of Ultraconserved Elements Yields Viable Mice JF - PLoS Biology VL - 5 IS - 9 SP - e234 N2 - Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability. KW - conservation KW - development KW - expression KW - rodents AU - Ahituv, Nadav AU - Zhu, Yiwen AU - Visel, Axel AU - Holt, Amy AU - Afzal, Veena AU - Pennacchio, Len AU - Rubin, Edward PY - 2007/09/01/ UR - http://dx.doi.org/10.1371/journal.pbio.0050234 ER -