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

被引：140

作者：

Housden, Benjamin E. ^{[1
]}

Muhar, Matthias ^{[2
]}

Gemberling, Matthew ^{[3
,4
]}

Gersbach, Charles A. ^{[3
,4
]}

Stainier, Didier Y. R. ^{[5
]}

Seydoux, Geraldine ^{[6
,7
]}

Mohr, Stephanie E. ^{[1
]}

Zuber, Johannes ^{[2
]}

Perrimon, Norbert ^{[1
,8
]}

机构：

[1] Harvard Med Sch, Dept Genet, 77 Ave Louis Pasteur

[2] Vienna Bioctr VBC, Res Inst Mol Pathol IMP, A-1030 Vienna, Austria

[3] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA

[4] Duke Univ, Ctr Genom & Computat Biol, Durham, NC 27708 USA

[5] Max Planck Inst Heart & Lung Res, Dept Dev Genet, 43 Ludwigstr, D-61231 Bad Nauheim, Germany

[6] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 725 North Wolfe St, Baltimore, MD 21218 USA

[7] Howard Hughes Med Inst, 725 North Wolfe St, Baltimore, MD 21218 USA

[8] Howard Hughes Med Inst, 77 Ave Louis Pasteur, Boston, MA 02115 USA

来源：

NATURE REVIEWS GENETICS | 2017年 / 18卷 / 01期

基金：

美国国家科学基金会; 美国国家卫生研究院; 欧洲研究理事会; 奥地利科学基金会;

关键词：

DOUBLE-STRANDED-RNA; ONE-STEP GENERATION; WIDE CRISPR SCREEN; GENOME-WIDE; CAENORHABDITIS-ELEGANS; HUMAN-CELLS; C; ELEGANS; INSERTIONAL MUTAGENESIS; AURORA-B; TRANSCRIPTIONAL ACTIVATION;

D O I：

10.1038/nrg.2016.118

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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, morphotinos 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.

引用

页码：24 / 40

页数：17

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