Document Detail

Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse.
MedLine Citation:
PMID:  10036219     Owner:  NLM     Status:  MEDLINE    
The aryl hydrocarbon receptor (AHR) is a transcriptional regulatory protein that binds to upstream DNA response elements of target genes. Activation of the AHR by binding of ligands such as polyhalogenated dioxins, furans, and PCBs is associated with a wide range of adverse biological outcomes, including cancer, immune deficiencies, embryo/fetotoxicity, and reproductive toxicity. Investigations of the diverse biological responses mediated by the AHR led to production of a transgenic mouse in which the gene coding for the AhR was inactivated. AHR-deficient mice were fertile and at maturity exhibited immune system impairment and hepatic fibrosis. Our laboratory received several of these homozygous knockout (-/-) mice and mated them with wild-type (+/+) C57BL/6N mice to generate large numbers of heterozygotes (+/-). The -/- males were then mated with a total of 45 heterozygous +/- females. Offspring of these matings were genotyped and mated in all genotypic combinations. Although male and female -/- adults were fertile, the -/- females had difficulty maintaining conceptuses during pregnancy, surviving pregnancy and lactation, and rearing pups to weaning. Only 46% of the 39 pregnant -/- females successfully raised pups to weaning. The -/- pups showed poor survival during lactation (average death rate per litter was 16%) and after weaning (26.5% of the 230 weaned -/- pups died within 2 weeks). Only 39% of the implantations in uteri of -/- dams resulted in offspring surviving to Postnatal Day 45. Across all litters the sex ratios and genotypic frequencies were comparable to expected values. Reproductive success was adversely affected in Ahr-null females and conceptuses. Additional study is needed to reveal the etiology of these effects.
B D Abbott; J E Schmid; J A Pitt; A R Buckalew; C R Wood; G A Held; J J Diliberto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  155     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-16     Completed Date:  1999-03-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  62-70     Citation Subset:  IM    
Reproductive Toxicology Division, National Health Effects and Environmental Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
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MeSH Terms
Embryo Implantation
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Aryl Hydrocarbon / deficiency*,  physiology
Reg. No./Substance:
0/Receptors, Aryl Hydrocarbon

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