Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach

囊胚基因分型用于小鼠突变档案的质量控制:一种符合伦理道德且经济实惠的方法

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作者:Ferdinando Scavizzi, Edward Ryder, Stuart Newman, Marcello Raspa, Diane Gleeson, Hannah Wardle-Jones, Lluis Montoliu, Almudena Fernandez, Marie-Laure Dessain, Vanessa Larrigaldie, Zuzana Khorshidi, Reetta Vuolteenaho, Raija Soininen, Philippe André, Sylvie Jacquot, Yi Hong, Martin Hrabe de Angelis, 

Abstract

With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects.

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