Related Experiment Video
Updated: Aug 7, 2026
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
The constitutively active Ah receptor (CA-Ahr) mouse as a potential model for dioxin exposure--effects in vital
Sara Brunnberg1, Patrik Andersson, Maria Lindstam
1Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Solna, Stockholm, Sweden. sara.brunnberg@ki.se
Abstract:
The dioxin/aryl hydrocarbon receptor (AhR) mediates most, if not all, toxic effects of dioxins and functions as a ligand-activated transcription factor regulating transcription of a battery of genes. In order to study the mechanisms behind the toxicity of ligands of the Ah receptor we have created a transgenic mouse model expressing a constitutively active Ah receptor (CA-AhR). The mutant Ah receptor is expressed and functionally active in all organs studied. The purpose of the present study was to characterize histopathologically, the phenotype of the CA-AhR with regard to the liver, kidney, lung, heart, spleen and thymus of male and female transgenic CA-AhR mice. Moreover, cell-specific activity of the CA-AhR using up-regulation of the AhR target gene CYP1A1 as a marker, was also examined. The relative weight of liver, kidney and heart were increased while relative thymus weight was decreased. Furthermore, slight morphological lesions of the liver, kidney and spleen was seen. Expression of CYP1A1 was found in cells corresponding to endothelial cells in all of the organs studied. In some tissues additional cell types, such as hepatocytes, renal tubuli cell and Clara cells expressed CYP1A1. Both the effects on organ weights and the cellular expression of CYP1A1 in CA-AhR mice correspond well to observations in TCDD-exposed mice. In conclusion, this characterization further support that the CA-AhR mouse is a useful model for life-long continuous low-level activity of the AhR, i.e. the dioxin exposure situation of humans of the general population.
Insights
A new transgenic mouse model with a constitutively active aryl hydrocarbon receptor (CA-AhR) mimics dioxin exposure effects. This model is valuable for studying long-term, low-level dioxin toxicity relevant to human populations.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor mediating dioxin toxicity.
- Understanding AhR's role in toxicity requires models that mimic continuous low-level exposure.
- Existing models often focus on acute high-dose exposures, not chronic low-level scenarios.
Purpose of the Study:
- To histopathologically characterize the phenotype of a constitutively active AhR (CA-AhR) transgenic mouse model.
- To examine the cell-specific activity of CA-AhR using CYP1A1 as a marker.
- To assess the utility of the CA-AhR mouse model for studying dioxin-like compound toxicity.
Main Methods:
- Creation of a transgenic mouse model expressing a constitutively active AhR (CA-AhR).
- Histopathological examination of liver, kidney, lung, heart, spleen, and thymus in male and female CA-AhR mice.
- Analysis of AhR target gene CYP1A1 expression to determine cell-specific activity.
Main Results:
- Increased relative weights of liver, kidney, and heart; decreased thymus weight observed.
- Slight morphological lesions noted in the liver, kidney, and spleen.
- CYP1A1 expression identified in endothelial cells across organs, and in hepatocytes, renal tubuli cells, and Clara cells in specific tissues.
Conclusions:
- The CA-AhR mouse model exhibits organ weight changes and CYP1A1 expression patterns similar to TCDD-exposed mice.
- Cell-specific CYP1A1 expression in the CA-AhR model reflects known AhR target cells.
- The CA-AhR mouse is a suitable model for investigating the effects of life-long, low-level AhR activity, mirroring human dioxin exposure.
