Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes

Cell. 2013 Jul 18;154(2):452-64. doi: 10.1016/j.cell.2013.06.022.


Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP:

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease / genetics
  • Disease Models, Animal
  • Female
  • Genes, Essential
  • Genetic Techniques*
  • Genome-Wide Association Study
  • Male
  • Mice
  • Mice, Knockout*
  • Phenotype*