Breeding of TRAMP mice for development of novel diagnostic imaging protocols: 2021-2022

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The TRAMP mice have been genetically modified to express the SV40T antigen under transcriptional control of the PB promotor, leading to specific expression in prostate epithelial cells. Consequently, the mice develop dysplastic lesions in the prostate, which progress to adenocarcinomas. Morphologically, the lesions resemble human prostate cancer. The model is therefore widely used for studies of progression of prostate cancer both on a molecular and a functional level. Furthermore, the onset of disease can be modified by dietary restriction or chemoprevention.

Intention of the study:
The intention of this project is to maintain the TRAMP colony at NTNU (continuation of FOTS 8092) for future studies of prostate cancer, in particular development of novel imaging protocol for prostate cancer diagnostics. This application is concerns breeding of TRAMP mice, with medical imaging included as a tool to monitor disease progression when required.

Expected inconvenience for the mice:
The TRAMP mice gradually develops prostate cancer through increasing degree of epithelial cell neoplasia. Normally, no signs of clinically significant prostate cancer is observed before the animals reach 30 weeks of age. Here, mice are not kept longer than needed for maintenance of the breeding colony, and are normally euthanised before the onset of any symptomatic prostate cancer. Hence, the mice included in the breeding program are only expected to experience none to mild discomfort associated with their prostatic phenotype.

Expected benefit for the society:
Prostate cancer is the cancer with highest incidence in men, and a significant portion of the health service resources is allocated to management of this patient group. There are large unmet medical needs both in primary diagnosis, risk stratification and follow-up of patients with suspected recurrence. Implementation of MR imaging in the standardised management plan is a step in the right direction, but improved diagnostic tools are still needed to optimise care for individual patients. For testing and validation of new techniques, the TRAMP mice offers an advantage as they imaging-wise resembles human prostate cancer.

Number of mice:
We intend to keep 3-6 breeding pairs at all times, indicating a yearly average of 50 mice for maintenance of a small colony.

RRR:
In order to eliminate discomfort for the mice, we will use MR or ultrasound imaging to screen for rare, aggressive forms of prostate cancer and/or severe prostatic hyperplasia in all mice that may be kept in the breeding program beyond 30 weeks of age.