Multiple research groups have tested petide-human Fc fusion proteins in mouse models, with no apparent adverse effects. However, I can't find any information on the difference between using human Fc and mouse Fc in a mouse model, particularly with relation to a peptide-hFc fusion protein.
This will vary from case to case, but in general, if you treat a mouse with a human Fc fusion molecule, the mice with develop a mouse anti-human immune response (MAHA) after approximately 12 to 14 days of exposure- developing both IgM and IgG antibodies against the treatment. Those antibodies may neutralie your fusion molecule or dramatically reduce the molecul's half-life. If your treatment exposure/study will be shorter than 12 days, you should be fine, but for more chronic studies, you'd be safer with a mouse F-fusion. That said, even murine Fc fusions can be rejected.
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