Confounding factors from inducible systems for spatiotemporal gene expression regulation

Author:

Wüst Rob C.I.12ORCID,Houtkooper Riekelt H.1ORCID,Auwerx Johan3ORCID

Affiliation:

1. Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences and Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands

2. Laboratory for Myology, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

3. Laboratory for Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Abstract

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We highlight some of these adverse effects, including whole-body endocrinology and disturbances in the gut microbiome and in mitochondrial and metabolic function.

Funder

ZonMw

Ecole Polytechnique Federale de Lausanne

Publisher

Rockefeller University Press

Subject

Cell Biology

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