Cited by 152Pharmacogenetics and Drug MetabolismAnimal Genetics and ReproductionCRISPR and Genetic Engineering

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ahr null alleles: distinctive or different?

Lahvis, Garet P, Bradfield, Christopher A·1998·Biochemical Pharmacology

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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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In vivo up-regulation of aryl hydrocarbon receptor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a dioxin-resistant rat model☆1☆Portions of this work were presented at the 20th International Symposium on Halogenated Environmental Organic Pollutants & POPS, Monterey, California (August 13–17, 2000).1Abbreviations: AHR, aryl hydrocarbon receptor; AP, alkaliSne phosphatase; ARNT, aryl hydrocarbon receptor nuclear translocator protein; dNTP, 2′-deoxynucleoside 5′-triphosphate; DRE, dioxin responsive element; H/W, Han/Wistar (Kuopio); L-E, Long-Evans (Turku AB); PCB, polychlorinated biphenyl; PCR, polymerase chain reaction; RT, reverse transcription; SD, Sprague Dawley; and TCDD, 2,3,7,8-tetrachlorodibenzo-pdioxin.
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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).”
ResultSelf-citation
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Authors: Lahvis, G. P., & Bradfield, C. A.
Affiliations: University of Wisconsin–Madison (US)
Corresponding author: Bradfield, Christopher A
ORCID: Lahvis, Garet P
Bradfield, Christopher A
Venue: Biochemical Pharmacology
Publisher: Elsevier BV
Published: 1998-10
Volume: 56
Issue: 7
Pages: 781-787
ISSN: 0006-2952 (ISSN-L)
DOI: 10.1016/s0006-2952(98)00134-8
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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ahr null alleles: distinctive or different?

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