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RIAD mice - colony maintenance

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1. Purpose: The purpose of this application/project is to breed and maintain the transgenic RIAD mice model. Several other projects (FOTs application) use these mice in studies linking the cAMP immunomodulatory pathway in T cells to Tumor immune evasion and obesity.

2. Adverse effects: The RIAD mice are viable and do not display serious abnormalities. Female RIAD mice are infertile (EOPW11Tg). Peripheral T cells from the RIAD mice display an enhanced T cell responsiveness and are less sensitive to cAMP mediated inhibition of immune function.

3. Expected utility: The RIAD mice are a unique tool to study the cAMP immunomodulatory signaling pathway in T cells. These mice can thus be used in studies of chronic infections, cancer and possibly also in obesity.

4. Species and number of animals: In total this application seeks approval for the use of 1600 mice.

5. The 3Rs: We want to study the involvment of the cAMP signaling pathway in T cells in complex context like chronic infection and cancer, processes that are too complex to be studied solely in cell culture and therefore needs to be carried out in these mice. However, we will limit the number of animals that are bred for colony maintenance by keeping only a small number (2-3) of breeding pairs going per substrain and may temporarily stop these breeding pairs if we reach sufficient numbers of offspring carrying RIAD constructs for future breeding without continuous breeding. Breeding lines in Limited use are cryopreserved. Mice will be housed in cages containing environmental enrichment, be housed on a 12-hour light/12-hour dark schedule and receive food ad libitum.