B6.129S5-Mtor^{Gt(OST92090)Lex}/J

Stock number: 013190
Research areas: Cancer Research, Developmental Biology Research, Research Tools

Description

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.

Detailed description

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.

Development

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

Symbol: Mtor^{Gt(OST92090)Lex}
Name: gene trap OST92090, Lexicon Genetics
MGI accession ID: MGI:3529989
Generation method: Gene trapped
Attributes: Reporter; Null/Knockout
Synonyms: Frap1^{Gt(neo)299Lex}; mTOR^-
Marker symbol: Mtor
Marker name: mechanistic target of rapamycin kinase
Marker synonyms: 2610315D21Rik; FKBP-rapamycin-associated protein FRAP; flat; FRAP; Frap1; FRAP2; mechanistic target of rapamycin (serine/threonine kinase); RAFT1; RAPT1; SKS
Chromosome: 4
Strain of origin: 129S5/SvEvBrd
Molecular note: The gene trapping vector containing a neo cassette was inserted into intron 1 at position 488.