title: Loss-of-function genetic tools for animal models: cross-species and cross-platform differences.
abstract: 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.
authors: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors: Benjamin E
authors: BE
authors: Housden
authors: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna 1030, Austria.
authors: Matthias
authors: M
authors: Muhar
authors: Department of Biomedical Engineering and the Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA.
authors: Matthew
authors: M
authors: Gemberling
authors: Department of Biomedical Engineering and the Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA.
authors: Charles A
authors: CA
authors: Gersbach
authors: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 43 Ludwigstrasse, Bad Nauheim 61231, Germany.
authors: Didier Y R
authors: DY
authors: Stainier
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21218, USA.|Howard Hughes Medical Institute, 725 North Wolfe Street, Baltimore, Maryland 21218, USA.
authors: Geraldine
authors: G
authors: Seydoux
authors: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors: Stephanie E
authors: SE
authors: Mohr
authors: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna 1030, Austria.
authors: Johannes
authors: J
authors: Zuber
authors: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors: Norbert
authors: N
authors: Perrimon
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D020868:Gene Silencing; D005838:Genotype; D006801:Humans; D023421:Models, Animal; D060172:Morpholinos / Q000494:pharmacology*; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D034622:RNA Interference; D013045:Species Specificity
chemical_list: D060172:Morpholinos