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Updated: Aug 11, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Transgenic mouse with high Cre recombinase activity in all prostate lobes, seminal vesicle, and ductus deferens
Chengliu Jin1, Kerstin McKeehan, Fen Wang
1Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030-3303, USA.
Background:
Prostate-specific gene ablation provides a powerful tool for functional characterization of genes that have impact on embryonic development or on other organs, specifically in the prostate. Uniform expression of Cre with high recombinase activity in the prostate is needed for prostate-specific gene ablation based on Cre-loxP recombinations. Currently, available strains of Cre transgenic mice only express Cre recombinase adequately in certain lobes of the prostate. In other lobes, the expression is low and mosaic. Additional strains of transgenic mice expressing high levels of prostate-specific Cre in all prostate lobes would be useful to study the impact of genome manipulation in all prostate lobes.
Methods:
The ARR2PB composite promoter with improved capacity to drive androgen-responsive gene expression was used to initiate expression of a transgene bearing the cDNA encoding a recently modified Cre recombinase with improved recombination activity. In addition, an insulator element from the chicken globin locus that minimized negative effect on transcription of the transgene imposed by chromosome structure was employed. The derived transgenic founders were crossed with the Z/AP reporter mouse and Fgfr2(f/f) mice bearing loxP flanking the FGFR2 locus. Immunochemical and mRNA analyses were employed to test expression and efficacy of the Cre recombinase in the prostate and other tissues.
Results:
The ARR2PBi-Cre transgenic mouse specifically and uniformly expressed Cre recombinase in the dorsal, lateral, ventral, and anterior lobes of the prostate, seminal vesicles, and ductus deferens. The Cre recombinase in these tissues effectively excised loxP flanked DNA fragments in the Z/AP reporter that triggered expression of beta-galactosidase, and the loxP-flanked FGFR2(f/f) locus resulting in specific ablation of FGFR2 in the prostate.
Conclusions:
Compared with the currently available prostate-specific Cre strains, the new ARR2PBi-Cre strain exhibited higher and more uniform expression of Cre recombinase in the prostate as well as in seminal vesicles and ductus deferens. This provides an additional tool for efficient hormone-dependent gene targeting in epithelial cells of all lobes of the adult prostate, seminal vesicle, and ductus deferens.
Insights
A new transgenic mouse model, ARR2PBi-Cre, enables uniform and efficient gene targeting in all prostate lobes. This tool aids in studying gene function and developing therapies for prostate diseases.
Area of Science:
- Genetics
- Molecular Biology
- Reproductive Biology
Background:
- Prostate-specific gene ablation is crucial for understanding gene function in prostate development and disease.
- Existing Cre transgenic mouse models show limited or mosaic Cre recombinase expression in prostate lobes.
- A need exists for mouse models with uniform, high-level prostate-specific Cre expression for comprehensive gene targeting.
Purpose of the Study:
- To develop a novel transgenic mouse model for efficient and uniform prostate-specific gene ablation.
- To characterize the expression pattern and recombination activity of a new Cre recombinase driver in the prostate.
Main Methods:
- Utilized the ARR2PB composite promoter and an insulator element to drive a modified Cre recombinase transgene.
- Generated transgenic founders and crossed them with Z/AP reporter and Fgfr2(f/f) mice.
- Assessed Cre recombinase expression and excision efficacy via immunochemical and mRNA analyses.
Main Results:
- The ARR2PBi-Cre mouse model demonstrated specific and uniform Cre recombinase expression across all prostate lobes, seminal vesicles, and ductus deferens.
- Effective excision of loxP-flanked DNA was confirmed in reporter mice and in the Fgfr2 locus, leading to gene ablation.
- Achieved high and consistent Cre recombinase activity throughout the targeted tissues.
Conclusions:
- The ARR2PBi-Cre strain offers superior and uniform Cre recombinase expression compared to existing models.
- This new tool facilitates efficient, hormone-dependent gene targeting in epithelial cells of the adult prostate, seminal vesicles, and ductus deferens.
- Provides a valuable resource for advancing research in prostate biology and disease.
