Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development
Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development
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DOI：
10.1073/pnas.93.13.6731
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发表时间：
1996-06-25
影响因子：
11.1
通讯作者：
Bradfield, CA
中科院分区：
文献类型：
--
作者：
Schmidt, JV;Su, GHT;Bradfield, CA
Ah受体（AHR）是一种配体激活的转录因子，介导对环境污染物如苯并[a]芘和2，3，7，8-四氯二苯并-p-二恶英的多效性反应。为了深入了解AHR的生理作用并开发用于风险评估的模型，使用基因靶向通过同源重组来灭活小鼠Ahr基因。Ahr（-1-）小鼠是可存活和可生育的，但显示出一系列肝脏缺陷，表明AHR在正常肝脏生长和发育中的作用。Ahr（-1-）表型在0-3周龄之间最严重，涉及早期生长缓慢和肝脏缺陷，包括肝脏重量减轻、短暂性微泡脂肪变性、髓外造血延长和门静脉细胞过多伴增厚和纤维化。
The Ah receptor (AHR) is a ligand-activated transcription factor that mediates a pleiotropic response to environmental contaminants such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. In an effort to gain insight into the physiological role of the AHR and to develop models useful In risk assessment, gene targeting was used to inactivate the murine Ahr gene by homologous recombination. Ahr(-1-) mice are viable and fertile but show a spectrum of hepatic defects that indicate a role for the AHR in normal liver growth and development. The Ahr(-1-) phenotype is most severe between 0-3 weeks of age and involves slowed early growth and hepatic defects, including reduced liver weight, transient microvesicular fatty metamorphosis, prolonged extramedullary hematopoiesis, and portal hypercellularity with thickening and fibrosis.