Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality
Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality
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DOI：
10.1074/jbc.m705471200
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发表时间：
2007-12-07
影响因子：
4.8
通讯作者：
Bradfield, Christopher A.
中科院分区：
文献类型：
--
作者：
Lin, Bernice C.;Sullivan, Ruth;Bradfield, Christopher A.
芳香烃受体相关蛋白9，ARA9（也称为XAP 2或AIP 1），是一种分子伴侣，与某些外源性受体（如芳香烃受体（AHR）和过氧化物酶体增殖物激活受体α（PPAR α））复合。为了更好地理解ARA9在异生物质信号转导中的作用之外的生理作用，我们在小鼠中的Ara9位点产生了无效等位基因。该基因纯合缺失的小鼠在整个胚胎发育过程中的不同时间点死亡。胚胎死亡伴随着头部和四肢血流减少，以及一系列心脏变形，包括右心室双出口，心室间隔缺损和心包水肿。在Ara9缺失小鼠中观察到的早期心血管缺陷表明ARA9蛋白在心脏发育中起重要作用。Ara9基因敲除小鼠中的发育畸变与Ahr或Ppar α处破坏的等位基因所观察到的发育畸变不同，这一观察结果表明ARA9在心脏发育中的作用不依赖于其与已知异生物素受体伴侣的相互作用。
The aryl hydrocarbon receptor-associated protein 9, ARA9 ( also known as XAP2 or AIP1), is a chaperone that is found in complexes with certain xenobiotic receptors, such as the aryl hydrocarbon receptor (AHR) and the peroxisome proliferator-activated receptor alpha(PPAR alpha). In an effort to better understand the physiological role of ARA9 outside of its role in xenobiotic signal transduction, we generated a null allele at the Ara9 locus in mice. Mice with a homozygous deletion of this gene die at various time points throughout embryonic development. Embryonic lethality is accompanied by decreased blood flow to head and limbs, as well as a range of heart deformations, including double outlet right ventricle, ventricular-septal defects, and pericardial edema. The early cardiovascular defects observed in Ara9-null mice suggest an essential role for the ARA9 protein in cardiac development. The observation that the developmental aberrations in Ara9-null mice are distinct from those observed for disrupted alleles at Ahr or Ppar alpha indicates that the role of ARA9 in cardiac development is independent of its interactions with its known xenobiotic receptor partners.