Cell
Volume 154, Issue 2, 18 July 2013, Pages 452-464
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Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes

https://doi.org/10.1016/j.cell.2013.06.022Get rights and content
Under a Creative Commons license
open access

Highlights

  • Large openly available resource of targeted mouse mutants and phenotypic data

  • Screen for broad range of disease features and traits

  • Many novel phenotypes suggest functions for both studied and unstudied genes

  • Haploinsufficiency and pleiotropy are common

Summary

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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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.

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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A full list of The Sanger Institute Mouse Genetics Project contributors may be found in the Supplemental Information