Honors College Thesis

 

Characterization of a Transgenic Mouse for Human Cytochrome P450 1B1 (CYP1B1) Public Deposited

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https://ir.library.oregonstate.edu/concern/honors_college_theses/bz60cz491

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  • Cytochrome P450 1B1 (Cyp1B1) is a xenobiotic metabolizing enzyme, responsible for polycyclic aromatic hydrocarbon (PAH) oxidative metabolism. CYP1B1 metabolically activates several species of environmentally relevant procarcinogenic PAHs to reactive carcinogens. PAHs are aryl hydrocarbon receptor (AhR) agonists, leading to CYP1B1 upregulation. Though CYP1B1 is highly conserved across species, wild type mouse Cyp1b1 differs from human CYP1B1 in several ways resulting in only 5 of the 11 xenobiotic responsive elements found in mouse being conserved in humans. We hypothesized that a transgenic “humanized” CYP1B1 mouse model can be useful for studying human-like metabolism of carcinogenic, or suspected carcinogenic compounds, such as PAHs, in exposure related disease. A wild type control mouse (B6129SF1 female x 129S male) was used as a positive control for native mouse expression. Mixed litters containing experimental hemizyogous CYP1B1 and negative control Cyp1b1 null mice were generated by crossing hemizygous CYP1B1 females (on a Cyp1b1/null background) with Cyp1b1 null males. Genotypes were determined experimentally via PCR and mRNA expression in tissue types (gonad, thymus, lung, liver) was determined via qRT-PCR. Potential applications of this model include translation to human risk from environmental contaminant exposure. Key Words: transgenic mouse model, polycyclic aromatic hydrocarbon, cytochrome P4501B1, aryl hydrocarbon receptor
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  • description.provenance : Submitted by Hyekyoung You (youhye@oregonstate.edu) on 2016-07-22T08:14:00ZNo. of bitstreams: 1You Hyekyoung 2016.pdf: 1543246 bytes, checksum: 16e6af6de278c7cc767d6cf47213655b (MD5)
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