STOCK Gt(ROSA)26Sor^{tm1(Notch1)Dam}/J

Stock number: 008159
Research areas: Cell Biology Research, Research Tools

Description

When used in conjunction with a Cre recombinase-expressing strain, these Rosa^N1-IC (or Rosa^Notch) mutant mice may be useful in generating conditional mutations for studying the effects of Notch pathway activation.

Detailed description

These mice contain a sequence encoding an intracellular portion of the mouse Notch1 gene (amino acids 1749-2293), but lacking the c-terminal PEST domain, and Green Fluorescent Protein, GFP, inserted into the GT(ROSA)26Sor locus. Expression of the Notch1 fragment and GFP is blocked by a loxP-flanked STOP fragment placed between the coding sequence and the GT(ROSA)26Sor promoter. The GFP expression is localized to the nucleus by an IRES sequence. The truncated cytoplasmic fragment encoded by the Notch1 sequence causes constitutive signaling activity. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants for studying the effects of Notch pathway activation. Homozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

For example, when crossed to a strain expressing a tamoxifen inducible Cre recombinase in all cells that express Shh (see Stock No. 005623), this mutant mouse strain may be useful in studies of Notch signaling.

When crossed to a strain expressing a tamoxifen inducible Cre recombinase in all cells that express Neurog3 such as spermatogonia and pancreatic islets cells (see Stock No. 008119), this mutant mouse strain may be useful in studies of Notch signaling.

When bred to a strain expression interferon inducible Cre recombinase in liver and lymphocytes (see Stock No. 003556 for example), this mutant mouse strain may be useful in studies of Notch signaling in lymphocyte development.

Development

A targeting vector containing a loxP- flanked neo-STOP cassette, mouse Notch1 sequence encoding amino acids 1749-2293 and GFP was inserted into the GT(ROSA)26Sor locus. The construct was introduced into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into receipient blastocysts. Resulting chimeric male animals were crossed to C57BL/6 females. The mice were then crossed to C57BL/6J for an unknown number of generations and maintained on the outbred ICR background.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(Notch1)Dam}
Name: targeted mutation 1, Douglas A Melton
MGI accession ID: MGI:2684314
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Reporter; Inserted expressed sequence
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: 129S4/SvJaeSor
Expressed genes: Notch1,notch 1,mouse, laboratory
Molecular note: A targeting vector containing a floxed neo cassette followed by a mouse Notch1 sequence fragment and GFP was inserted at the endogenous locus. Excision of the floxed neo cassette leads to the expression of the Notch1 sequence encoding an intracellular portion of NOTCH1 (amino acids 1749-2293), but lacking the c-terminal PEST domain. IRES preceded the sequence encoding the nuclear-localized enhanced GFP.
General note: Phenotypic Similarity to Human Syndrome: Liposarcoma, Dedifferentiated J:237232 in double Gt(ROSA)26Sor^{tm1(Notch1)Dam} and Tg(Adipoq-cre)1Evdr mutants.

Phenotypic Similarity to Human Syndrome: Osteosclerosis J: 233131 in double Gt(ROSA)26Sor^{tm1(Notch1)Dam} and Tg(Col1a1-cre)1Kry mutants.