In this strain, the allele replaces alternate exon 1 and common exon 2 of the regulatory associated protein of mTOR (Mechanistic target of rapamycin), complex 1 (Rptor) gene with an internal ribosome entry site (IRES)-lacZ (β-galactosidase), and a neomycin resistance (neo) cassette, abolishing gene function. These mice may be useful for studying raptor-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
In this strain, the allele replaces alternate exon 1 and common exon 2 of the regulatory associated protein of mTOR (Mechanistic target of rapamycin), complex 1 (Rptor) gene with an internal ribosome entry site (IRES)-lacZ(β-galactosidase), and a neomycin resistance (neo) cassette, abolishing gene function. Heterozygous mice are viable, fertile, and normal in size, while homozygous mice die by e6.5. Raptor forms the complex mTORC1 with mLST8 (mTOR associated Protein, LST8 homolog) and mTOR, which is critical for the growth of the inner cell mass and trophoblast cell outgrowth during early embryonic development. When Raptor-/- blastocysts are implanted, 25% can implant but all fail to expand and differentiate. In culture, by day 4 the cells of the blastocysts stop growing and by day 7 the cells are detached and dying. β-gal staining is evident in embryonic cells expressing Raptor. These mice may be useful for studying raptor-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 targeting vector was designed to replace alternate exon 1 and common exon 2 of the regulatory associated protein of MTOR (Mechanistic target of rapamycin), complex 1 (Rptor) gene with an internal ribosome entry site (IRES)-lacZ (β-galactosidase) followed by a neomycin resistance (neo) cassette. The construct was electroporated into 129S5/SvEv-derived embryonic stem (ES) cells. The donating investigator reports that correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were backcrossed at least 8 times to C57BL/6 mice (see SNP note below) to generate a colony of Rptor+/- 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.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Lexicon Genetics|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Rptor, regulatory associated protein of MTOR, complex 1|
|Site of Expression||lacZ is expressed in embryonic cells expressing Raptor.|
|Strain of Origin||129S/SvEvBrd|
|Molecular Note||Alternate exon 1 and common exon 2 were replaced with an IRES-lacZ/neo cassette.|
When maintaining a live colony, heterozygous mice may be bred to wildtype littermates from the colony or C57BL/6J inbred mice (Stock No. 000664). Homozygous embryos die by e6.5.
When using the B6.129S5-Rptortm1Lex/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013191 in your Materials and Methods section.
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