Genetically manipulated mice: a powerful tool with unsuspected caveats
- 5 July 2007
- journal article
- review article
- Published by Wiley in The Journal of Physiology
- Vol. 582 (2), 481-488
- https://doi.org/10.1113/jphysiol.2007.134908
Abstract
Although genetic manipulations in mice have provided a powerful tool for investigating gene function in vivo, recent studies have uncovered a number of developmental phenomena that complicate the attribution of phenotype to the specific genetic change. A more realistic approach has been to modulate gene expression and function in a temporal and tissue-specific manner. The most common of these methods, the CreLoxP and tetracycline response systems, are surveyed here and their recently identified shortcomings discussed, along with a less well known system based on the E. coli lac operon and modified for use in mammals. The potential for further complications in interpretation due to hitherto unexpected epigenetic effects involving transfer of RNA or protein in oocytes or sperm is also explored. Given these problems we reiterate the necessity for the use of completely reversible methods that will allow each experimental group of animals to act as their own control. Using these methods with a number of specific modifications to eliminate non-specific effects from random insertion sites and inducer molecules, the full potential of genetic manipulation studies should be realized.Keywords
This publication has 43 references indexed in Scilit:
- Pharmacologic and Functional Characterization of Malignant Hyperthermia in the R163C RyR1 Knock-in MouseAnesthesiology, 2006
- RNA-mediated non-mendelian inheritance of an epigenetic change in the mouseNature, 2006
- Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1Nature Immunology, 2006
- Characterization of the First Nonmammalian T2 Cytokine Gene Cluster: The Cluster Contains Functional Single-Copy Genes for IL-3, IL-4, IL-13, and GM-CSF, a Gene for IL-5 That Appears to Be a Pseudogene, and a Gene Encoding Another Cytokinelike Transcript, KK34Journal of Interferon & Cytokine Research, 2004
- Visualization of the Dynamics of Gene Expression in the Living MouseMolecular Imaging, 2004
- Expression profiling reveals off-target gene regulation by RNAiNature Biotechnology, 2003
- Germline transmission of RNAi in miceNature Structural & Molecular Biology, 2003
- Ligand-Dependent Genetic Recombination in FibroblastsThe American Journal of Pathology, 2002
- Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice.Proceedings of the National Academy of Sciences, 1996
- Conditional gene targeting.JCI Insight, 1996