NOD/ShiLtJ-Ifih1^em1Ygch/HmtseJ

Stock number: 038785
Product name: Ifih1^KO
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

These Ifih1^KO mice contain a ZFN-mediated mutation that creates an out-of-frame 34bp deletion (AA 425-436) in MDA5. Female Ifih1^KO mice develop spontaneous Type 1 diabetes (T1D) similar to NOD mice while male Ifih1^KO mice have increased spontaneous T1D compared with NOD mice. These mice also develop Coxsackievirus B3 (CVB3)-accelerated T1D similar to NOD mice. These mice useful when studying the development and progression of type 1 diabetes (T1D).

Detailed description

These Ifih1^KO mice contain a ZFN-mediated mutation that creates an out-of-frame 34bp deletion resulting in a premature stop codon in exon 6 of the interferon induced with helicase C domain 1 gene. Also known as MDA5, Ifih1 encodes for a dsRNA sensor important for innate immune antiviral responses. Exon 6 encodes the helicase 1 domain of MDA5 which senses dsRNA, contains ATPase activity, and interacts with the caspase activation recruitment domain (CARD) to promote antiviral responses. This KO mutation does not lead to any detectable truncated MDA5 protein and completely lacks MDA5 function.

Female Ifih1^KO mice develop spontaneous Type 1 diabetes (T1D) similar to NOD mice while male Ifih1^KO mice have increased spontaneous T1D compared with NOD mice. These mice also develop Coxsackievirus B3 (CVB3)-accelerated T1D similar to NOD mice.

Homozygous mice are viable and fertile. Homozygous mice develop diabetes with a similar onset as NOD/ShiLtJ wildtype mice. A footpad injection of Complete Freund's Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders.

Of note, Ifih1^ΔHel1 mice (Stock No. 0038788) are a similar strain containing an in-frame 15bp deletion in exon 6 of MDA5. In Ifih1^ΔHel1 mice, MDA5 protein has reduced ATPase activity are mice are protected from spontaneous and CVB3-accelerated T1D.

Development

This zinc finger nuclease induced mutation targets exon 6 of the interferon induced with helicase C domain 1 (Ifih1) gene, creating an out-of-frame 34bp deletion (AA 425-436) resulting in a premature stop codon. The mRNA encoding the ZFN was injected into one cell embryos derived from NOD/ShiLtJ mice (Stock No. 001976) and one mouse was identified by PCR and bred back to a NOD/ShiLtJ mice. Resulting offspring were bred to NOD/ShiLtJ mice to develop a colony of Ifih1^KO mice. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize NOD/ShiLtJ oocytes.

Allele

Symbol: Ifih1^em1Ygch
Name: endonuclease-mediated mutation 1, Yi-Guang Chen
MGI accession ID: MGI:7523919
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
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: NOD/ShiLtJ
Molecular note: Zinc finger nuclease-mediated genome editing targets exon 6, creating an out-of-frame 34bp deletion (AA 425-436) resulting in a premature stop codon.