Tissue distribution and function of the Aryl hydrocarbon receptor repressor (AhRR) in C57BL/6 and Aryl hydrocarbon receptor deficient mice.
The Aryl hydrocarbon receptor repressor (AhRR) is a new member of bHLH-PAS proteins which is important in the regulation of cell growth and differentiation. The AhRR shares structural similarities with Aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT). The AhRR is thought to be involved in transcriptional control of AhR-regulated genes by sequestering ARNT. Most of the knowledge of regulation and function of the AhRR is from studies in cell lines. Here, we report the tissue distribution of AhRR in AhR deficient and wild type C57BL/6 mice. In addition, the inducibility of the AhRR and Cytochrome P450 (CYP) 1A1 in response to benzo(a)pyrene (B(a)P) (10 mg/kg bw i.p.) was investigated. The results show that the AhRR mRNA expression pattern in untreated C57BL/6 mice varies across tissues with high levels in hearts and brains. In other tissues, AhRR mRNA expression was low. In contrast to wild-type animals, the tissue levels in AhR-/- mice were about two to three orders of magnitude lower. Treatment of wild-type animals with B(a)P resulted in an induced AhRR expression in liver, spleen, lung and ovary. No significant induction of AhRR mRNA was found in brain and heart tissues, which have a constitutively high level of AhRR expression. Simultaneous measurements of CYP1A1 and AhRR mRNA expression do not strongly support the view that the AhRR tissue pattern triggers the tissue specific responsiveness of AhR-regulated genes to B(a)P treatment.
Bernshausen
Thorsten
T
Arbeitsgruppe Toxikologie, IUF, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Jux
Bettina
B
Esser
Charlotte
C
Abel
Josef
J
Fritsche
Ellen
E
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001564:Benzo(a)pyrene / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009153:Mutagens / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency* / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D051792:Basic Helix-Loop-Helix Proteins; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D018076:DNA, Complementary; D009153:Mutagens; D012313:RNA; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C117300:Ahrr protein, mouse