B6.129S(Cg)-Ddit3^tm2.1Dron/J

Stock number: 005530
Product name: CHOP KO
Research areas: Apoptosis Research, Cell Biology Research, Research Tools

Description

Mice that are homozygous for the targeted mutation have mouse embryonic fibroblasts and renal proximal tubular epithelial cells with decreased apoptosis in response to endoplasmic reticulum stress induced by the toxin, tunicamycin. This mutant mouse strain may be useful in studies of apoptosis and pathogenesis due to endoplasmic reticulum stress.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (MRNA or protein) is detected by Northern or Western blot analysis of toxin challenged mouse embryonic fibroblasts (MEFs). MEFs and renal proximal tubular epithelial cells have decreased apoptosis in response to endoplasmic reticulum stress induced by the toxin, tunicamycin. Pancreatic islets cells are more resistant to nitric oxide induced apoptosis. MEFs exhibit a delayed onset of unfolded protein response (UPR) target gene expression when treated with tunicamycin. This mutant mouse strain may be useful in studies of apoptosis and pathogenesis due to endoplasmic reticulum stress. The Donating Investigator reports that lacZ activity is not detected.

Development

A targeting construct containing a NLS-lacZ cassette and a floxed PGK-Neo cassette was used to disrupt almost all the coding region in exons 3 and 4. The construct was electroporated into 129S6/SvEvTac derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The floxed selection cassette was later removed by Cre recombinase excision by crossing the mice to a Cre deleter strain. The donating investigator stated that the resulting mice were then crossed to C57BL/6 mice (see SNP note below) for 5 generations.



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 26 of 27 markers throughout the genome suggested a C57BL/6 genetic background (1 segregating for 129 on Chromosome 1), one 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

Symbol: Ddit3^tm2.1Dron
Name: targeted mutation 2.1, David Ron
MGI accession ID: MGI:5441015
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Ddit3
Marker name: DNA-damage inducible transcript 3
Chromosome: 10
Strain of origin: 129S6/SvEvTac
Molecular note: A NLS-lacZ cassette and a floxed PGK-Neo cassette replaced the coding region in parts of exons 3 and 4. Cre-mediated recombination removed the neo cassette.