ArticleToxicological sciences : an official journal of the Society of Toxicology2008
The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 174 citations in OpenAlex.
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- Preserved and Accessible: Quantifying PFAS in Formalin-Fixed and Paraffin-Embedded Tissues for Retrospective Exposure and Dose Assessment.Environmental science & technology · 2026Article
- Organelle resilience as a comparative blueprint for longevity.EMBO molecular medicine · 2026Review
- Systematic evaluation of the evidence base on ethylCurrent research in toxicology · 2026Review
- Per- and polyfluorinated substances (PFAS) promote osteoclastogenesis and bone loss through PPARα activation.Toxicology reports · 2025Article
- Perfluorooctanoic acid increases serum cholesterol in a PPARα-dependent manner in female mice.Archives of toxicology · 2025Article
- Peroxisome Proliferator-Activated Receptor Alpha Stimulation Preserves Renal Tight Junction Components in a Rat Model of Early-Stage Diabetic Nephropathy.International journal of molecular sciences · 2024Article
- Fenofibrate-promoted hepatomegaly and liver regeneration are PPARActa pharmaceutica Sinica. B · 2024Article
- Rapid human genomic DNA cloning into mouse artificial chromosome via direct chromosome transfer from human iPSC and CRISPR/Cas9-mediated translocation.Nucleic acids research · 2024Article
- Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice.Toxicology · 2024Article
- The Role of Endocrine Disruptors Bisphenols and Phthalates in Obesity: Current Evidence, Perspectives and Controversies.International journal of molecular sciences · 2024Review
- Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues.International journal of molecular sciences · 2023Article
- Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.Toxicologic pathology · 2023Article
- YAP-TEAD mediates PPAR α-induced hepatomegaly and liver regeneration in mice.Hepatology (Baltimore, Md.) · 2022Article
- The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders.International journal of molecular sciences · 2021Review
- Oleuropein-Induced Acceleration of Cytochrome P450-Catalyzed Drug Metabolism: Central Role for Nuclear Receptor Peroxisome Proliferator-Activated Receptor α.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet.Toxicology and applied pharmacology · 2021Article
- Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic clone bred onto a ppar alpha-null mouse background, designated hPPAR alpha PAC. In hPPAR alpha PAC mice, the human PPAR alpha gene is expressed in tissues with high fatty acid catabolism and induced upon fasting, similar to mouse PPAR alpha in wild-type (Wt) mice. Upon treatment with the PP fenofibrate, hPPAR alpha PAC mice exhibited responses similar to Wt mice, including peroxisome proliferation, lowering of serum triglycerides, and induction of PPAR alpha target genes encoding enzymes involved in fatty acid metabolism in liver, kidney, and heart, suggesting that human PPAR alpha (hPPAR alpha) functions in the same manner as mouse PPAR alpha in regulating fatty acid metabolism and lowering serum triglycerides. However, in contrast to Wt mice, treatment of hPPAR alpha PAC mice with fenofibrate did not cause significant hepatomegaly and hepatocyte proliferation, thus indicating that the mechanisms by which PPAR alpha affects lipid metabolism are distinct from the hepatocyte proliferation response, the latter of which is only induced by mouse PPAR alpha. In addition, a differential regulation of several genes, including the oncogenic let-7C miRNA by PPs, was observed between Wt and hPPAR alpha PAC mice that may contribute to the inherent difference between mouse and human PPAR alpha in activation of hepatocellular proliferation. The hPPAR alpha PAC mouse model provides an in vivo platform to investigate the species difference mediated by PPAR alpha and an ideal model for human risk assessment PPs exposure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.