Abbott B D, Birnbaum L S, Perdew G H
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Dev Dyn. 1995 Oct;204(2):133-43. doi: 10.1002/aja.1002040204.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a basic region/helix-loop-helix (bHLH) motif. AhR has been sequenced and the functional domains defined and there is information on the formation of complexes with other peptides and interactions with DNA, although these areas continue to be investigated. AhR mediates many biological effects such as developmental toxicity, including induction of cleft palate and hydronephrosis. This regulatory protein is expressed in embryonic liver and has been immunohistochemically localized in cells of human and mouse secondary palate. The expression of AhR in embryonic tissues and its ability to disrupt development suggests a significant role for this protein in development. The present study examines the pattern of AhR expression in the C57BL/6N mouse embryo from gestation days (GD) 10-16, using in situ hybridization and immunohistochemical analysis. AhR mRNA was localized with 35S-RNA antisense riboprobe (cAh1 probe, 1.8 Kb amino terminal DNA). AhR protein was localized with purified monoclonal antibody (RPT-9) raised against the N-terminal peptide sequence. AhR mRNA and protein were expressed in GD 10-13 neuroepithelium, and as development progressed the levels in brain decreased. GD 10-12 embryos also showed AhR in branchial arches, heart, somites, and liver. AhR protein and mRNA in heart were highest at GD 10-11 and decreased with age. In liver, AhR mRNA and protein levels increased and nuclear localization became more pronounced with gestational age. In GD 14-16 embryos levels in liver and adrenal were highest, but AhR was present in ectoderm, bone, and muscle. AhR expression was specific for both cell type, organ/tissue, and developmental stage, suggesting that this novel ligand-activated transcriptional regulator may be important in normal embryonic development.
芳基烃受体(AhR)是一种具有碱性区域/螺旋-环-螺旋(bHLH)基序的配体激活转录因子。AhR已被测序,其功能结构域也已明确,并且有关于它与其他肽形成复合物以及与DNA相互作用的信息,尽管这些领域仍在研究中。AhR介导许多生物学效应,如发育毒性,包括诱导腭裂和肾积水。这种调节蛋白在胚胎肝脏中表达,并已通过免疫组织化学定位在人和小鼠次生腭的细胞中。AhR在胚胎组织中的表达及其破坏发育的能力表明该蛋白在发育中起重要作用。本研究使用原位杂交和免疫组织化学分析,检测了妊娠第10 - 16天C57BL/6N小鼠胚胎中AhR的表达模式。AhR mRNA用35S - RNA反义核糖探针(cAh1探针,1.8 Kb氨基末端DNA)进行定位。AhR蛋白用针对N末端肽序列产生的纯化单克隆抗体(RPT - 9)进行定位。AhR mRNA和蛋白在妊娠第10 - 13天的神经上皮中表达,随着发育进程,大脑中的水平下降。妊娠第10 - 12天的胚胎在鳃弓、心脏、体节和肝脏中也显示有AhR。心脏中的AhR蛋白和mRNA在妊娠第10 - 11天最高,并随年龄增长而下降。在肝脏中,AhR mRNA和蛋白水平随着胎龄增加而升高,并且核定位变得更加明显。在妊娠第14 - 16天的胚胎中,肝脏和肾上腺中的水平最高,但AhR也存在于外胚层、骨骼和肌肉中。AhR的表达在细胞类型、器官/组织和发育阶段方面都具有特异性,表明这种新型的配体激活转录调节因子可能在正常胚胎发育中起重要作用。