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Generation and Characterization of a CYP2A13‐Transgenic Mouse Model
Author(s) -
Jia Kunzhi,
Li Lei,
Liu Zhihua,
Kluetzman Kerri,
Zhang Qingyu,
Ding Xinxin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.892.5
Subject(s) - transgene , genetically modified mouse , clone (java method) , biology , respiratory tract , microbiology and biotechnology , gene , genetics , respiratory system , anatomy
CYP2A13, 2B6, and 2F1, neighboring P450 genes on human chromosome 19, are active toward many drugs, toxicants, and carcinogens. A CYP2A13/2B6/2F1‐transgenic mouse, in which CYP2A13 and 2F1 are both expressed in the respiratory tract, while CYP2B6 is expressed in the liver, was recently generated (Wei et al., Drug Metab. Dispos. 40:1144–1150, 2012). The aim of the present study is to generate a CYP2A13 (only) transgenic mouse, so that the specific activity of CYP2A13 can be determined. The CYP2B6 and 2F1 genes in the CYP2A13/2B6/2F1 genomic clone were inactivated via genetic manipulations, while 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 are normal in gross morphology, development, and fertility. As in the CYP2A13/2B6/2F1‐transgenic mouse, CYP2A13 expression in the 2A13‐TG mouse is limited to the respiratory tract; in contrast, CYP2B6 and 2F1 proteins are not detected. Additional studies using 2A13‐humanized (2A13‐TG/Cyp2abfgs‐null) mouse, produced by intercrossing between 2A13‐TG and newly generated Cyp2abfgs‐null mice, confirmed that the transgenic CYP2A13 is active in the bioactivation of NNK, a lung procarcinogen. The 2A13‐TG mouse should be valuable for assessing specific roles of human CYP2A13 in xenobiotic toxicity in the lung.