Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality.
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.
Lin
Bernice C
BC
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706, USA.
Sullivan
Ruth
R
Lee
Youngsook
Y
Moran
Susan
S
Glover
Edward
E
Bradfield
Christopher A
CA
D000818:Animals; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics; D005121:Extremities / Q000098:blood supply / Q000196:embryology; D017353:Gene Deletion; D006257:Head / Q000098:blood supply / Q000196:embryology; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D047493:PPAR alpha; D011506:Proteins; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; C103265:aryl hydrocarbon receptor-interacting protein