First Author | Wu Y | Year | 2019 |
Journal | Nat Commun | Volume | 10 |
Issue | 1 | Pages | 2883 |
PubMed ID | 31253768 | Mgi Jnum | J:278409 |
Mgi Id | MGI:6323732 | Doi | 10.1038/s41467-019-10748-2 |
Citation | Wu Y, et al. (2019) Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos. Nat Commun 10(1):2883 |
abstractText | 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. |