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

Jacqueline K White, Anna-Karin Gerdin, Natasha A Karp, Ed Ryder, Marija Buljan, James N Bussell, Jennifer Salisbury, Simon Clare, Neil J Ingham, Christine Podrini, Richard Houghton, Jeanne Estabel, Joanna R Bottomley, David G Melvin, David Sunter, Niels C Adams, David Tannahill, Darren Logan, Daniel G MacArthur, Jonathan FlintVinit B Mahajan, Stephen H Tsang, Ian Macleod Smyth, Fiona Watt, William C Skarnes, Gordon Dougan, David J Adams, Ramiro Ramirez-Solis, Allan Bradley, Karen Steel

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275 Citations (Scopus)

Abstract

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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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:
Original languageEnglish
Pages (from-to)452 - 464
Number of pages13
JournalCell
Volume154
Issue number2
DOIs
Publication statusPublished - 2013

Cite this

White, J. K., Gerdin, A-K., Karp, N. A., Ryder, E., Buljan, M., Bussell, J. N., Salisbury, J., Clare, S., Ingham, N. J., Podrini, C., Houghton, R., Estabel, J., Bottomley, J. R., Melvin, D. G., Sunter, D., Adams, N. C., Tannahill, D., Logan, D., MacArthur, D. G., ... Steel, K. (2013). Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes. Cell, 154(2), 452 - 464. https://doi.org/10.1016/j.cell.2013.06.022