Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов

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СКАЧАТЬ G A A A ‐ ‐ A A 0610031O16Rik 3 138,226,121 rs31386034 A C ~ C C ‐ ~ ~ 0610031O16Rik 3 138,226,125 rs31000950 C G G G G ‐ G G 0610031O16Rik 3 138,226,160 rs30901573 G ‐ ‐ ‐ A ‐ ‐ ‐ Adh7 3 138,226,410 rs31091615 A G* G* G* G* ‐ G* G* 0610031O16Rik 3 138,228,417 rs30262949 T C C C C ‐ C A 0610031O16Rik 3 138,228,503 rs50248152 G A A A A ‐ A G 0610031O16Rik 3 138,228,653 rs31428790 A G G G G ‐ G G 0610031O16Rik 3 138,228,722 rs30904366 A G G G G ‐ G G Adh7 3 138,231,370 ‐ T g ~ ‐ Adh7 3 138,231,388 rs50766077 C A A A A ‐ A A Adh7 3 138,231,410 rs46894990 A G G G G ‐ G G Adh7 3 138,231,427 rs46279078 T A A A A ‐ A A

Large Scale Mutagenesis

      International Mouse Phenotyping Consortium (IMPC; https://www.mousephenotype.org)

Many pharmaceutical companies have created large number of mutant mice, some using large scale, high throughput methods to both create and phenotype the mice generated. However, their goals were very drug oriented and proprietary. Only now, many years later are some of the results becoming publicly available from such projects as those done by Lexicon [46]. An alternative approach was to systematically create null mutations in all known protein‐coding genes in the mouse and utilize a systematic and standardized phenotyping protocol. The International Mouse Phenotyping Consortium (IMPC) was developed to meet this objective [47]. While initially a variety of recombineering methods were used, now null mutations are created using CRISPR/Cas9. The goal is to inactivate approximately 20 000 genes one at a time on a standardized inbred strain (C56BL/6N). Attempts at overall standardization enable comparison of results creating in a sense an encyclopedia on gene function inferred from knockout phenotypes. However, there are variations between the environments at different participating institutions and different substrains of C57BL/6N are used. For example, some use a substrain where the Crb1^rd8 allele causing a retinal phenotype in C57BL/6N mice was corrected using TALEN‐mediated homology‐directed repair [48]. This website provides deep summaries of the data by gene, together with primary data that is also accessible through the IMPC API web services. At the time of writing, 6440 knockouts have been phenotyped for more than 600 parameters in embryonic and adult life. A schematic of the phenotyping pipeline is shown in СКАЧАТЬ