Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

Abstract

This large international initiative is a major collaboration across 25 research institutes that was set up as part of the scientific community’s response to concerns regarding the notoriously poor reproducibility of scientific research. Up to now, many mouse gene knock-outs have been made and reported, but inconsistency between findings is widespread; this may arise due to bias in animal selection, focus on one sex or on one isogenic mouse background, or use of poor statistical methods. To address this, the International Mouse Phenotyping Consortium is performing systematic phenotyping of, eventually all, single gene knock-out mice. They study both males and females, at least 7 mice of each sex, and use a carefully standardised pipeline assessment of 509 phenotypes, covering diverse neurological, behavioral, metabolic, cardiovascular, pulmonary, reproductive, respiratory, sensory, musculoskeletal and immunological parameters. The findings are producing new models of mendelian diseases, novel mendelian disease candidate genes, and new functional knowledge of genes about which we knew very little – which is highly relevant and timely information in our current era of emerging whole exome/genome sequencing in our patients. Limitations include the focus on only adult phenotypes, and currently the database of genes is yet incomplete. But if you are interested in a particular gene, this online database is a great starting point http://www.mousephenotype.org/.