Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is a key downstream effector of mTOR complex 1 (mTORC1) that represses cap-dependent mRNA translation initiation by sequestering the translation initiation factor eIF4E. Reduced mTORC1 signaling is associated with life span extension and improved metabolic homeostasis. The Tg-4EBP1mt transgene has the CAGGS promoter/enhancer and a floxed GFP-3xSTOP cassette followed by a cDNA sequence encoding a constitutively active, mTORC1-nonresponsive mutant variant of human EIF4EBP1 harboring the mTOR phosphorylation site mutations T37A and T46A. In the absence of Cre recombinase, the donating investigator reports that Tg-4EBP1mt transgenic mice have widespread expression of GFP, and no 4EBP1mt expression. They note that GFP fluorescence is weak and suggest immunostaining to enhance the GFP signal. Hemizygous mice are viable and fertile with no observed behavioral or metabolic abnormalities. To date (April 2017), it has not been attempted to make mice homozygous for the Tg-4EBP1mt transgene. Following Cre recombinase exposure, the floxed-GFP-3xSTOP cassette is deleted - this results in expression of the constitutively active, mTORC1-nonresponsive 4EBP1mt. For example, when Tg-4EBP1mt are bred to Tg(Ckmm-cre)5Khn mice (see Stock No. <a href="https://www.jax.org/strain/006475">006475</a>) the resulting bigenic mice (called Tg-4EBP1mt-muscle mice) on C57BL/6J genetic background exhibit enhanced 4EBP1 activity in mouse skeletal muscle - this protected them against age- and diet-induced insulin resistance and metabolic rate decline. Bigenic animals also displayed increased energy expenditure (altered adipose tissue distribution, including reduced white adipose accumulation and preserved brown adipose mass) and were protected from hepatic steatosis.

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The Tg-4EBP1mt transgene has a floxed-GFP-3xSTOP cassette preventing expression of constitutively active, mTORC1-nonresponsive mutant variant of human EIF4EBP1. These mice may be useful for Cre recombinase-inducible studies involving mTOR complex 1 signaling and metabolism.

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