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

Journal Article (Review;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Housden, BE; Muhar, M; Gemberling, M; Gersbach, CA; Stainier, DYR; Seydoux, G; Mohr, SE; Zuber, J; Perrimon, N

Published Date

  • January 2017

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 24 - 40

PubMed ID

  • 27795562

Pubmed Central ID

  • PMC5206767

Electronic International Standard Serial Number (EISSN)

  • 1471-0064

International Standard Serial Number (ISSN)

  • 1471-0056

Digital Object Identifier (DOI)

  • 10.1038/nrg.2016.118


  • eng