B6.Cg-Ifih1^tm1.1Cln/J

Stock number: 015812
Product name: Mda-5-
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Virology Research

Description

These Ifih1 knock-out mice may be useful for studying immune responses to viruses and other pathogens.

Detailed description

A targeting vector was designed to delete exon1 and 400 bp of upstream sequence of the interferon induced with helicase C domain 1 Ifih1 gene in order to abolish gene function. Homozygous mice are viable and fertile. Ifih1, an intracellular sensor of dsRNA, activates various immune cell types, including NK cells, after viral infection. Ifih1 detects dsRNAs that penetrate into the cytosol of the cell and transmits signal through accessory cells inducing IFN-α and IFN-β production. Homozygous mutant mice exhibit a decrease in NK cell activation and a decrease in IFN-γ production after treatment with Poly (I:C), an analogue of viral dsRNA. These mice may be useful for studying immune responses to viruses and other pathogens.

Development

A targeting vector was designed to replace of exon1, and 400 bp of upstream sequence, of the interferon induced with helicase C domain 1 (Ifih1 or Mda5) gene with a loxP-flanked neomycin (neo) resistance cassette. The construct was electroporated into 129X1/SvJ-derived SSC10 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054) to remove the neo cassette. The donating investigator reported that the resulting offspring were backcrossed to C57BL/6J mice (see SNP note below) for at least 6 generations to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (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, 2 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: Ifih1^tm1.1Cln
Name: targeted mutation 1.1, Marco Colonna
MGI accession ID: MGI:3663677
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Mda-5^-; MDA5^-
Marker symbol: Ifih1
Marker name: interferon induced with helicase C domain 1
Marker synonyms: 9130009C22Rik; AGS7; Helicard; Hlcd; IDDM19; IMD95; MDA5; MDA-5; RGD1560496; RLR-2; SGMRT1
Chromosome: 2
Strain of origin: 129X1/SvJ
Molecular note: A targeting vector was designed to replace exon 1 and 400 bp of upstream sequence with a floxed MC1-neo cassette. Cre mediated excision removed the MC1-neo, leaving a single loxP site.