Loss-of-function genetic tools for animal models: cross-species and cross-platform differences

Benjamin E. Housden, Matthias Muhar, Matthew Gemberling, Charles A. Gersbach, Didier Y.R. Stainier, Geraldine Seydoux, Stephanie E. Mohr, Johannes Zuber, Norbert Perrimon

Research output: Contribution to journalReview articlepeer-review


Our understanding of the genetic mechanisms that underlie biological processes has relied extensively on loss-of-function (LOF) analyses. LOF methods target DNA, RNA or protein to reduce or to ablate gene function. By analysing the phenotypes that are caused by these perturbations the wild-type function of genes can be elucidated. Although all LOF methods reduce gene activity, the choice of approach (for example, mutagenesis, CRISPR-based gene editing, RNA interference, morpholinos or pharmacological inhibition) can have a major effect on phenotypic outcomes. Interpretation of the LOF phenotype must take into account the biological process that is targeted by each method. The practicality and efficiency of LOF methods also vary considerably between model systems. We describe parameters for choosing the optimal combination of method and system, and for interpreting phenotypes within the constraints of each method.

Original languageEnglish (US)
Pages (from-to)24-40
Number of pages17
JournalNature Reviews Genetics
Issue number1
StatePublished - Dec 13 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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