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Targeted Disruption of the α Isoform of the Peroxisome Proliferator-Activated Receptor Gene in Mice Results in Abolishment of the Pleiotropic Effects of Peroxisome Proliferators
Open accessAbstract
To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted the ligand-binding domain of the alpha isoform of mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for the mutation lack expression of mPPAR alpha protein and yet are viable and fertile and exhibit no detectable gross phenotypic defects. Remarkably, these animals do not display the peroxisome proliferator pleiotropic response when challenged with the classical peroxisome proliferators, clofibrate and Wy-14,643. Following exposure to these chemicals, hepatomegaly, peroxisome proliferation, and transcriptional-activation of target genes were not observed. These results clearly demonstrate that mPPAR alpha is the major isoform required for mediating the pleiotropic response resulting from the actions of peroxisome proliferators. mPPAR alpha-deficient animals should prove useful to further investigate the role of this receptor in hepatocarcinogenesis, fatty acid metabolism, and cell cycle regulation.
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Sáez-Orellana, F., Leroy, T., Ribeiro, F., Kreis, A., Leroy, K., Lalloyer, F., Baugé, E., Staels, B., Duyckaerts, C., Brion, J.-P., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.150099 · Cited by 29
Role of Redox Imbalance in the Molecular Mechanisms Responsible for Immunosenescence
Daynes, R. A., Enioutina, E. Y., & Jones, D. C. (2003) · Antioxidants & Redox Signaling · doi:10.1089/152308603770310185 · Cited by 27
CYTOCHROME P450 KNOCKOUT MICE: NEW TOXICOLOGICAL MODELS
McKinnon, R. A., & Nebert, D. W. (1998) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1998.tb02153.x · Cited by 22
Metadata
- Authors
- Lee, S. S.-T., Pineau, T., Drago, J., Lee, E. J., Owens, J. W., Kroetz, D. L., Fernandez-Salguero, P. M., Westphal, H., & Gonzalez, F. J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1995-06-01
- Volume
- 15
- Issue
- 6
- Pages
- 3012-3022
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2121914083
- Cited by
- 1,655
- References
- 4
- FWCI
- 18.83
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
