Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-9-4
pubmed:abstractText
The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals. Both receptors regulate the expression of genes involved in the biotransformation of chemicals in a ligand-dependent manner. As the ligand specificity of PXR and CAR have diverged between species, the prediction of in vivo PXR and CAR interactions with a drug are difficult to extrapolate from animals to humans. We report the development of what we believe are novel PXR- and CAR-humanized mice, generated using a knockin strategy, and Pxr- and Car-KO mice as well as a panel of mice including all possible combinations of these genetic alterations. The expression of human CAR and PXR was in the predicted tissues at physiological levels, and splice variants of both human receptors were expressed. The panel of mice will allow the dissection of the crosstalk between PXR and CAR in the response to different drugs. To demonstrate the utility of this panel of mice, we used the mice to show that the in vivo induction of Cyp3a11 and Cyp2b10 by phenobarbital was only mediated by CAR, although this compound is described as a PXR and CAR activator in vitro. This panel of mouse models is a useful tool to evaluate the roles of CAR and PXR in drug bioavailability, toxicity, and efficacy in humans.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10037683, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10473093, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10529899, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10628745, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10748001, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10757780, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10801973, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-10935643, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-11248085, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-11283262, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-11602521, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12067248, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12372848, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12376703, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12413960, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12611900, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-12799447, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-14567971, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-14907713, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-14977869, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-15109949, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-15322232, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-15347657, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-15774478, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-16253141, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-16556603, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-16877263, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-16894644, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-17093002, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-17194715, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-1736885, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-17442842, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-3058117, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-3827847, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-3875783, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-5571904, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-7300821, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-7560060, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-7628309, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-8082563, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-8114692, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-8435079, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-8521508, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-9727070, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-9770465, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-9771703, http://linkedlifedata.com/resource/pubmed/commentcorrection/18677425-9784494
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3228-39
pubmed:dateRevised
2010-9-22
pubmed:meshHeading
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