Immune System Impairment and Hepatic Fibrosis in Mice Lacking the Dioxin-Binding Ah Receptor
Open accessAbstract
The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr -/- ) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr -/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr -/- mice were reduced in size by 50 percent and showed bile duct fibrosis. Ahr -/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds. Thus, the AHR plays an important role in the development of the liver and the immune system.
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Hepatic phenotypes, including reduced liver size, hepatic portal fibrosis, neonatal hepatic steatosis, and reduced hepatocyte size, were also observed in Ahr null mice.
“Hepatic phenotypes, including reduced liver size, hepatic portal fibrosis, neonatal hepatic steatosis, and reduced hepatocyte size, were also observed (Fernandez-Salguero et al., 1995; Harstad et al., 2006).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Fernandez-Salguero et al., 1995
The liver-comparison passage reports smaller livers and portal-tract fibrosis in Ahr-null mice, and the Fig. 2 caption describes small hepatocytes with little cytoplasm. Our copy does not report neonatal hepatic steatosis, so this source supports three of the four listed phenotypes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe generation of three independent Ahr null mouse models (AhrΔ1, AhrΔ2, and AhrLacZ) has revealed a significant role for the AHR in hepatic and vascular development as well as for the maintenance of barrier tissues and the immune system.
“The generation of three independent Ahr null mouse models (AhrΔ1, AhrΔ2, and AhrLacZ) described in more detail below, has revealed a significant role for the AHR in hepatic and vascular development as well as for the maintenance of barrier tissues (e.g., intestine, skin, and lung) and the immune system (Fernandez-Salguero et al., 1995; Mimura et al., 1997; J. V. Schmidt et al., 1996).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Fernandez-Salguero et al., 1995
The Ahr-deficient mouse-line description and the liver and immune-system findings support this paper's contribution to the cited sentence. The liver histology and immune-cell passages report hepatic fibrosis and reduced peripheral lymphocytes, but this paper describes one mouse line, not all three models; it does not establish vascular development or maintenance of barrier tissues. Its organ survey reports no obvious histological abnormalities in the intestine or lung (section labels: “Abstract,” “Ahr+I+ mice,” and organ comparison; page numbers unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredGenetic tools such as the Ahr null mouse model have revealed an essential role of AHR in normal physiology.
“Genetic tools such as the Ahr null mouse model have revealed an essential role of AHR in normal physiology (Fernandez-Salguero et al., 1995; Mimura et al., 1997; J. V. Schmidt et al., 1996).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Fernandez-Salguero et al., 1995
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“AhrD1null mouse The AhrD1 mouse harbors a neomycin resistance gene driven by the PGK promoter (NeoPGK) in place of exon-1 at the Ahr locus (Figure 4, Table 2; Fernandez-Salguero et al. 1995).”
BackgroundInfluential
- Authors
- Fernandez-Salguero, P., Pineau, T., Hilbert, D. M., McPhail, T., Lee, S. S. T., Kimura, S., Nebert, D. W., Rudikoff, S., Ward, J. M., & Gonzalez, F. J.
- Affiliations
- National Institutes of Health (US)
- Venue
- Science
- Published
- 1995-05-05
- Volume
- 268
- Issue
- 5211
- Pages
- 722-726
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2091726431
- Cited by
- 1,075
- References
- 0
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 15 · 2023: 23 · 2022: 28 · 2021: 34 · 2020: 26 · 2019: 28 · 2018: 33 · 2017: 45 · 2016: 40 · 2015: 25 · 2014: 26 · 2013: 30 · 2012: 36
- FWCI
- 56.29
- Type
- journal article
- Language
- en
- Open access
- green
- hal.inrae.fr
- Licence
- cc-by-nc
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc)
- Funders
- National Institute of Environmental Health Sciences (R01ES006811, P30ES006096)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- aryl hydrocarbon receptor, AhR knockout mice, immune system development, lymphocyte accumulation, liver fibrosis, bile duct fibrosis, dioxins, liver development, xenobiotic metabolism, embryonic lethality
- MeSH terms
- Animals, Female, Gene Expression Regulation, Immunity, Liver, Liver Cirrhosis, Experimental, Lymphoid Tissue, Male, Mice, Inbred C57BL, Receptors, Aryl Hydrocarbon, Mice, Knockout, Mice
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