ArticlePloS one2013
Mice with chimeric livers are an improved model for human lipoprotein metabolism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
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- A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B.Communications biology · 2023Article
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- Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice.Molecular psychiatry · 2022Article
- Fibroblast growth factor 15/19 expression, regulation, and function: An overview.Molecular and cellular endocrinology · 2022Review
- Article
- Liver-humanized mice: A translational strategy to study metabolic disorders.Journal of cellular physiology · 2022Review
- Generation of Human Liver Chimeric Mice and Harvesting of Human Hepatocytes from Mouse Livers.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Aberrant FGFR4 signaling worsens nonalcoholic steatohepatitis in FGF21KO mice.International journal of biological sciences · 2021Article
- In Vivo Functional Analysis of Nonconserved Human lncRNAs Using a Humanized Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans.Hepatology (Baltimore, Md.) · 2020Article
- Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab.JACC. Basic to translational science · 2020Article
- Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice.Seminars in liver disease · 2020Review
- Animal models to study bile acid metabolism.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.Journal of lipid research · 2018Article
- Animal Models to Study Hepatitis C Virus Infection.Frontiers in immunology · 2018Review
Corrections and comments
- Erratum issuedNauglers, Scott [corrected to Naugler, Willscott Edward]
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveRodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism.
designFRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR.
resultsChimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal.
conclusionHumanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.
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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.