B6.129X1-Notch1^tm2Rko/GridJ

Stock number: 007181
Product name: Notch1^flox
Research areas: Cell Biology Research, Developmental Biology Research, Research Tools

Description

When bred to mice with a Cre recombinase gene, exon 1 of the targeted gene is deleted in the cre expressing tissue(s); these conditional knockout mice may be useful in generating early neural progenitor cell-specific mutants. This mutant strain may be useful in studies such as apoptosis in neural development and loss of Notch1 heterozygosity.

Detailed description

Mice homozygous for this "floxed" Notch1 allele (fN1) are viable and fertile. These mice possess loxP sites on either side of exon 1 of the targeted gene. When bred to mice with a Cre recombinase gene, exon 1 of the targeted gene is deleted in the cre expressing tissue(s). These conditional knockout mice may be useful in generating tissue-specific mutants for studying the development of a wide range of tissues: for example, when crossed to a strain expressing Cre recombinase primarily in the nervous system (see Stock No. 003771), this mutant strain may be useful in studies of apoptosis in neural development.

When crossed to a strain expressing a differential Cre mediated reporter protein labeling: Notch1 signaling in actively cycling stem/progenitor cells (see Stock No. 006953), this mutant strain may be useful in studies of loss of Notch1 heterozygosity.

When bred to mice carrying Tg(Wnt1-cre)11Rth (Stock No. 009107), Cre recombinase expression in the midbrain and developing neural tube results in postnatal lethality.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting construct was designed to place a loxP-flanked PGK-neo cassette upstream of exon 1 of the targeted gene, as well as a single loxP site in intron 1. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre recombinase vector to remove the selection cassette. The resulting ES cells harboring the loxP-flanked exon 1 were injected into blastocysts to generate chimeric mice. Mutant mice were then sent to Dr. Thomas Gridley (The Jackson Laboratory) in 2003 on an unspecified mixed genetic background. These mice were supplied to The Jackson Laboratory Repository (as Stock No. 006951) in 2007. After this, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 007181).

Allele

Symbol: Notch1^tm2Rko
Name: targeted mutation 2, Raphael Kopan
MGI accession ID: MGI:3044585
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Notch1
Marker name: notch 1
Chromosome: 2
Strain of origin: 129X1/SvJ
Molecular note: LoxP were inserted flanking the first coding exon of the gene. An adjacent loxP flanked neomycin cassette was removed by Cre-mediated recombination in ES cells prior to production of chimeric animals.