This secretory trap mutation abolishes endogenous mTOR (Mechanistic target of rapamycin) gene function and expresses a neomycin (neo) resistance cassette/simian virus 40 (SV40) polyadenylylation signal fusion protein. Heterozygous mice are viable, fertile, and normal in size, while homozygous mice die by e6.5. mTOR forms the complex mTORC1 with mLST8 (mTOR associated protein (LST8 homolog)) and Rptor (regulatory associated protein of mTOR, complex 1), which is critical for the growth of the inner cell mass and trophoblast cell outgrowth during early embryonic development. mTOR also forms the complex mTORC2 with mLST8 and Rictor (Rptor independent companion of mTOR, complex 2), which is critical for midgestational embryonic development. The inner cell mass and trophoblast giant cells fail to expand in explanted mTOR-/- blastocysts. By day 4 the cells of the blastocysts stop growing and by day 7 the cells are detached and dying. These mice may be useful for studying mTOR complex signaling associated with cell growth, cell proliferation/differentiation, cell survival, cancer, diabetes, aging, tuberous sclerosis complex (TSC), lymphangioleiomyomatosis (LAM), Cowden disease, Peutz-Jeghers syndrome (PJS), neurofibromatosis, and familial cardiac hypertrophy.
