ahr null alleles: distinctive or different?
Abstract
Two independent laboratories have generated Ahr "null" or "knockout" mice that share some common characteristics but also have distinct phenotypes. In this Commentary, we will discuss our view of the candidate variables that might account for these differences. More importantly, we hope that this discussion can identify important parameters to be assessed by investigators in the process of characterizing their own modified loci. The variables that we have considered include the possibility that different targeting strategies can result in altered products with unsuspected function or that the targeting event itself can alter the function of neighboring genes. Further, genetic background can have an important influence on phenotype, and differences in genome can be introduced during derivation by the type of embryonic stem cells used and by the random segregation of parental genes in the F2 generation of line propagation. In addition, phenotype may be acutely sensitive to environmental variables, such as pathogen and chemical exposure and stress introduced by crowding and disease. Finally, we discuss approaches to resolving differences between null mice and propose a partial solution, the institution of a repository for detailed information on targeted alleles that may not typically be allowed in today's "fast paced" scientific publications.
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Despite initial inconsistent reports, the three Ahr null alleles produce quite similar phenotypes, with variation attributable to genetic background, environmental variables, or distinct laboratory emphasis.
“Despite inconsistent reports in initial characterization of these three models, subsequent examination of these alleles has indicated that all phenotypes are in fact quite similar and the variation is due to genetic background, environmental variables, or distinct laboratory emphasis (Lahvis & Bradfield, 1998).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis & Bradfield, 1998
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“…reports in initial characterization of these three models, subsequent examination of these alleles has indicated that all phenotypes are in fact quite similar and the variation is due to genetic background, environmental variables, or distinct laboratory emphasis (Lahvis and Bradfield 1998).”
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- Authors
- Lahvis, G. P., & Bradfield, C. A.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Bradfield, Christopher A
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 56
- Issue
- 7
- Pages
- 781-787
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2131562982
- Cited by
- 152
- References
- 25
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 2 · 2014: 5 · 2013: 8 · 2012: 9
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p30ca007175-36)
- National Cancer Institute (P30 CA 07175)
- National Institute of Environmental Health Sciences (ES06883, R01ES006883)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- aryl hydrocarbon receptor, knockout mice, genetic background effects, embryonic stem cell derivation, phenotypic variability
- MeSH terms
- Alleles, Animals, Crosses, Genetic, Models, Biological, Pedigree, Phenotype, Receptors, Aryl Hydrocarbon, Mice, Knockout, Mice
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