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. 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.
David Sabatini, Whitehead Institute
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.
A "secretory trap" targeting vector was used replace the endogenous Mechanistic target of rapamycin (mTOR) targeted gene with a neomycin (neo) resistance cassette followed by the simian virus 40 polyadenylylation signal. This gene trap targeting vector integrated into intron 1 at base position 488 of the mTOR locus via electroporation into 129S5/SvEvBrd-derived Lex-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were backcrossed at least 8 times to C57BL/6 mice to generate a colony of mTOR+/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||gene trap OST92090, Lexicon Genetics|
|Allele Type||Gene trapped|
|Allele Synonym(s)||Frap1Gt(neo)299Lex; mTOR-|
|Gene Symbol and Name||Mtor, mechanistic target of rapamycin kinase|
|Strain of Origin||129S5/SvEvBrd|
|Molecular Note||The gene trapping vector containing a neo cassette was inserted into intron 1 at position 488.|
|Mutations Made By|| |
David Sabatini, Whitehead Institute
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or C57BL/6J inbred mice (Stock No. 000664). Homozygous embryos die by e6.5.
When using the B6.129S5-MtorGt(OST92090)Lex/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013190 in your Materials and Methods section.
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