deletion of ultraconserved elements yields viable mice删除ultraconserved元素收益率可行的老鼠.pdfVIP

PLoS BIOLOGY Deletion of Ultraconserved Elements Yields Viable Mice 1,2¤ 1 1 1 1 1,2 1,2* Nadav Ahituv , Yiwen Zhu , Axel Visel , Amy Holt , Veena Afzal , Len A. Pennacchio , Edward M. Rubin 1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 2 United States Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America 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 doe