Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality
| Autor: | Susan M. Moran, Youngsook Lee, Bernice C. Lin, Christopher A. Bradfield, Ruth Sullivan, E.W.N. Glover |
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| Rok vydání: | 2007 |
| Předmět: |
Heart Defects
Congenital Embryonic Development Biochemistry Xenobiotics chemistry.chemical_compound Mice Animals PPAR alpha Allele Receptor Molecular Biology Gene Mice Knockout biology Intracellular Signaling Peptides and Proteins Proteins Extremities Heart Cell Biology Aryl hydrocarbon receptor Null allele Cell biology chemistry Receptors Aryl Hydrocarbon Chaperone (protein) biology.protein Embryo Loss Signal transduction Xenobiotic Head Gene Deletion Molecular Chaperones Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 282(49) |
| ISSN: | 0021-9258 |
| Popis: | 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 (PPARalpha). 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 Pparalpha indicates that the role of ARA9 in cardiac development is independent of its interactions with its known xenobiotic receptor partners. |
| Databáze: | OpenAIRE |
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