Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development.
Proc Natl Acad Sci U S A
; 101(47): 16677-82, 2004 Nov 23.
Article
em En
| MEDLINE
| ID: mdl-15545609
ABSTRACT
The aryl hydrocarbon receptor (AHR) is commonly known for its role in the adaptive metabolism of xenobiotics and in the toxic events that follow exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Previously, we have demonstrated that the AHR and its heterodimeric partner, the AHR nuclear translocator (ARNT), play a role in the developmental closure of a hepatic vascular shunt known as the ductus venosus (DV). To investigate the mechanism of DV closure, we generated hypomorphic alleles of the Ahr and Arnt loci. Using these models, we then asked whether this vascular defect could be rescued by receptor activation during late development. By manipulating gestational exposure, the patent DV in AHR or ARNT hypomorphs could be efficiently closed by dioxin exposure as early as embryonic day 12.5 and as late as embryonic day 18.5. These findings define the temporal regulation of receptor activation during normal ontogeny and provide evidence to support the idea that receptor activation and AHR-ARNT heterodimerization are essential for normal vascular development. Taken in the broader context, these data demonstrate that similar AHR signaling steps govern all major aspects of AHR biology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Vasos Sanguíneos
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Receptores de Hidrocarboneto Arílico
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Proteínas de Ligação a DNA
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Dibenzodioxinas Policloradas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article