title: Generation and characterization of a novel CYP2A13--transgenic mouse model.
abstract: CYP2A13, CYP2B6, and CYP2F1 are neighboring cytochrome P450 genes on human chromosome 19, and the enzymes that they encode overlap in substrate specificity. A CYP2A13/2B6/2F1-transgenic mouse, in which CYP2A13 and 2F1 are both expressed in the respiratory tract and CYP2B6 is expressed in the liver, was recently generated. We generated a CYP2A13 (only) transgenic mouse so that the specific activity of CYP2A13 can be determined. The CYP2B6 and CYP2F1 genes in the CYP2A13/2B6/2F1 genomic clone were inactivated via genetic manipulations, and CYP2A13 was kept intact. A CYP2A13 (only) transgenic (2A13-TG) mouse was generated using the engineered construct and then characterized to confirm transgene integrity and determine copy numbers. The 2A13-TG mice were normal in gross morphology, development, and fertility. As in the CYP2A13/2B6/2F1-transgenic mouse, CYP2A13 expression in the 2A13-TG mouse was limited to the respiratory tract; in contrast, CYP2B6 and 2F1 proteins were not detected. Additional studies using the CYP2A13-humanized (2A13-TG/Cyp2abfgs-null) mouse produced by intercrossing between 2A13-TG and Cyp2abfgs-null mice confirmed that the transgenic CYP2A13 is active in the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a lung procarcinogen. The 2A13-TG mouse should be valuable for assessing specific roles of human CYP2A13 in xenobiotic toxicity in the respiratory tract.
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Kunzhi
authors.initials: K
authors.lastname: Jia
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hartog
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Kerri
authors.initials: K
authors.lastname: Kluetzman
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York xding@albany.edu.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ding
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism*; D012137:Respiratory System / Q000201:enzymology / Q000378:metabolism
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human