Tissue-specific consequences of tag fusions on protein expression in transgenic mice.

ABSTRACT: Genetic fusion of protein tags is widely used to study protein functions in vivo. It is well known that tag fusion can cause unwanted changes in protein stability, but whether this is an inherent property of the tagged protein, or can be influenced by the cell and tissue environment, is unclear. Using a series of genome edited mouse models, we show that tag-dependent changes in protein expression can vary across different primary cell and tissue contexts. In one case (Ncaph2), a C-terminal auxin-inducible degron fusion strongly increased protein stability in some tissues but decreased it in others. Destabilisation resulted from tissue-specific 'leakage' of the auxin-inducible degron, which depended on TIR1 expression, and occurred selectively in the small intestine where basal concentratio

SUBMITTER: Taylor GCA 

PROVIDER: S-EPMC12407551 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature