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Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos.


ABSTRACT: A substantial number of mouse genes, about 25%, are embryonically lethal when knocked out. Using current genetic tools, such as the CRISPR-Cas9 system, it is difficult-or even impossible-to produce viable mice with heritable embryonically lethal mutations. Here, we establish a one-step method for microinjection of CRISPR reagents into one blastomere of two-cell embryos to generate viable chimeric founder mice with a heritable embryonically lethal mutation, of either Virma or Dpm1. By examining founder mice, we identify a phenotype and role of Virma in regulating kidney metabolism in adult mice. Additionally, we generate knockout mice with a heritable postnatally lethal mutation, of either Slc17a5 or Ctla-4, and study its function in vivo. This one-step method provides a convenient system that rapidly generates knockout mice possessing lethal phenotypes. This allows relatively easy in vivo study of the associated genes' functions.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC6599060 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos.

Wu Yi Y   Zhang Jing J   Peng Boya B   Tian Dan D   Zhang Dong D   Li Yang Y   Feng Xiaoyu X   Liu Jinghao J   Li Jun J   Zhang Teng T   Liu Xiaoyong X   Lu Jing J   Chen Baian B   Wang Songlin S  

Nature communications 20190628 1


A substantial number of mouse genes, about 25%, are embryonically lethal when knocked out. Using current genetic tools, such as the CRISPR-Cas9 system, it is difficult-or even impossible-to produce viable mice with heritable embryonically lethal mutations. Here, we establish a one-step method for microinjection of CRISPR reagents into one blastomere of two-cell embryos to generate viable chimeric founder mice with a heritable embryonically lethal mutation, of either Virma or Dpm1. By examining f  ...[more]

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