Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes
Cet article présente les premiers résultats du projet "Sanger Institute Mouse Genetics" qui vise à produire de façon systématique des lignées de modèles murins dans lesquels un gène a été invalidé et à identifier les phénotypes associés
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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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.
"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
More than 900 new mutant mice lines and a multifaceted phenotypic screening platform reveal unanticipated pleiotropies, widespread effects of haploinsufficiency, potential disease models, and functions for unstudied genes.
Cell , article en libre accès, 2012