Induction of the Cyp1a-1 dioxin-responsive enhancer in transgenic mice.

AUTOR(ES)

Jones, S N

RESUMO

Cyp1a-1, whose product, aryl hydrocarbon hydroxylase, assists in detoxification of polycyclic aromatic hydrocarbons, is the best characterized of the murine cytochrome P450 genes. The Cyp1a-1 dioxin-responsive enhancer region has been previously analyzed in vitro and found to induce expression of heterologous genes upon exposure of transfected cells to various aromatic hydrocarbons. A 2.58 kbp DNA fragment containing the Cyp1a-1 enhancer elements and promoter region was coupled to the chloramphenicol acetyltransferase (CAT) reporter gene and used to create transgenic mice. CAT assays were performed on tissues harvested from three different lines of transgenic mice following mock-induction or induction using the aromatic hydrocarbon, 3-methylcholanthrene. Basal levels of expression were detected in the spleen and small bowel of non-induced mice, with little or no expression detected in the liver. Treatment with 3-methylcholanthrene increased hepatic expression levels by as much as 10,000-fold. More modest levels of induction were also recorded in the spleen, small bowel, kidney, and lung. The results indicate that the dioxin-responsive enhancer region functions as a strongly inducible promoter in vivo. Differences in the response to induction between male and female mice suggest that Cyp1a-1 expression may be governed in a gender related manner.

Documentos Relacionados

• Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer.
• Control of cytochrome P1-450 gene expression: analysis of a dioxin-responsive enhancer system.
• In situ protein-DNA interactions at a dioxin-responsive enhancer associated with the cytochrome P1-450 gene.
• Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation.
• Tissue specificity of a glucocorticoid-dependent enhancer in transgenic mice.