Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Generation and characterization of a novel CYP2A13--transgenic mouse model.

Literature DB >> 24907355

Generation and characterization of a novel CYP2A13--transgenic mouse model.

Kunzhi Jia¹, Lei Li¹, Zhihua Liu¹, Matthew Hartog¹, Kerri Kluetzman¹, Qing-Yu Zhang¹, Xinxin Ding².

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.

Entities: Chemical Disease Gene Species

Mesh：

Substances：

Year: 2014 PMID： 24907355 PMCID： PMC4109209 DOI： 10.1124/dmd.114.059188

Source DB: PubMed Journal: Drug Metab Dispos ISSN： 0090-9556 Impact factor: 3.922

31 in total

1. Development of a real-time polymerase chain reaction-based method for the measurement of relative allelic expression and identification of CYP2A13 alleles with decreased expression in human lung.

Authors: Xiuling Zhang; Michele Caggana; Tracey L Cutler; Xinxin Ding
Journal: J Pharmacol Exp Ther Date: 2004-06-02 Impact factor: 4.030

2. Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb.

Authors: X X Ding; M J Coon
Journal: Mol Pharmacol Date: 1990-04 Impact factor: 4.436

3. Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Authors: T Su; Z Bao; Q Y Zhang; T J Smith; J Y Hong; X Ding
Journal: Cancer Res Date: 2000-09-15 Impact factor: 12.701

Review 4. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.

Authors: Xinxin Ding; Laurence S Kaminsky
Journal: Annu Rev Pharmacol Toxicol Date: 2002-01-10 Impact factor: 13.820

Review 5. Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

Authors: Stephen S Hecht
Journal: Nat Rev Cancer Date: 2003-10 Impact factor: 60.716

6. Role of CYP2A13 in the bioactivation and lung tumorigenicity of the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: in vivo studies using a CYP2A13-humanized mouse model.

Authors: Vandana Megaraj; Xin Zhou; Fang Xie; Zhihua Liu; Weizhu Yang; Xinxin Ding
Journal: Carcinogenesis Date: 2013-08-05 Impact factor: 4.944

Review 7. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.

Authors: David R Nelson; Darryl C Zeldin; Susan M G Hoffman; Lois J Maltais; Hester M Wain; Daniel W Nebert
Journal: Pharmacogenetics Date: 2004-01

8. Pyridyloxobutyl DNA adducts inhibit the repair of O6-methylguanine.

Authors: L A Peterson; X K Liu; S S Hecht
Journal: Cancer Res Date: 1993-06-15 Impact factor: 12.701

9. Establishment of an efficient BAC transgenesis protocol and its application to functional characterization of the mouse Brachyury locus.

Authors: Kuniya Abe; Masaaki Hazama; Hideki Katoh; Ken-ichi Yamamura; Misao Suzuki
Journal: Exp Anim Date: 2004-07

10. Organization and evolution of the Cyp2 gene cluster on mouse chromosome 7, and comparison with the syntenic human cluster.

Authors: Haoyi Wang; Kyle M Donley; Diane S Keeney; Susan M G Hoffman
Journal: Environ Health Perspect Date: 2003-11 Impact factor: 9.031

7 in total

7. Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.

Authors: Minghui Ji; Yudong Zhang; Na Li; Chao Wang; Rong Xia; Zhan Zhang; Shou-Lin Wang
Journal: Int J Environ Res Public Health Date: 2017-10-13 Impact factor: 3.390

7 in total

Generation and characterization of a novel CYP2A13--transgenic mouse model.

1. Development of a real-time polymerase chain reaction-based method for the measurement of relative allelic expression and identification of CYP2A13 alleles with decreased expression in human lung.

2. Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb.

3. Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Review 4. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.

Review 5. Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

6. Role of CYP2A13 in the bioactivation and lung tumorigenicity of the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: in vivo studies using a CYP2A13-humanized mouse model.

Review 7. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.

8. Pyridyloxobutyl DNA adducts inhibit the repair of O6-methylguanine.

9. Establishment of an efficient BAC transgenesis protocol and its application to functional characterization of the mouse Brachyury locus.

10. Organization and evolution of the Cyp2 gene cluster on mouse chromosome 7, and comparison with the syntenic human cluster.

Review 1. P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.

2. Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice.

3. Regulation of Fgf15 expression in the intestine by glucocorticoid receptor.

4. Generation and characterization of a monoclonal antibody against human BCL6 for immunohistochemical diagnosis.

Review 5. Genetic and Enzymatic Characteristics of CYP2A13 in Relation to Lung Damage.

6. aflN Is Involved in the Biosynthesis of Aflatoxin and Conidiation in Aspergillus flavus.

7. Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.