B6(Cg)-Sting1^tm1.2Camb/J

Stock number: 025805
Product name: MPYS^- , STING^-
Strain synonyms: STING^-
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

MPYS^-/- (STING KO) mice may be useful for studying cytosolic detection of pathogen DNA, the innate immune response and exploring aspects of the tumor microenvironment.

Detailed description

MPYS^-/- (STING KO) mice lack exons 3-5 of the transmembrane protein 173 (Tmem173) gene. MPYS acts as a facilitator of innate immune signaling and interferon beta (IFNβ) production through the detection of cytosolic bacterial pathogens and their cyclic dinucleotide metabolites. Mice that are homozygous for this allele are viable and fertile. MPYS^-/- mice produce less IFNβ and interleukin-6 (IL6) after 8 hours of infection with Listeria monocytogenes or Francisella tularensis than controls, with normal production seen by 24 hours. MPYS^-/- mice produce more IFNβ than the Sting1^goldenticket mice (Stock No. 017537) which do not produce IFNβ after Listeria monocytogenes infection.



In 2020, a 48 SNP (single nucleotide polymorphism) panel analysis showed that one of the 43 markers, in the Rd8 gene on Chromosome 1, was segregating. This mutation has been associated with retinal degeneration.

Development

A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette followed by a loxP site downstream of exon 5, and a second loxP site upstream of exon 3 of the transmembrane protein 173 (Tmem173) gene. The construct was electroporated into C57BL/6N-A^tm1Brd-derived JM8A3. N1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting offspring were bred with albino C57BL/6-Tg(CAG-Flpo)1Afst mice to remove the neo cassette, and progeny were subsequently bred to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. 006054) to remove the floxed exons. Mice lacking the FLP and Cre expressing transgenes were sent to The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

In 2020, a 48 SNP (single nucleotide polymorphism) panel analysis showed that one of the 43 markers was segregating: the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. Colony managers are actively breeding this SNP mutation out of this colony by backcrossing to C57BL/6J mice.

Allele

Symbol: Sting1^tm1.2Camb
Name: targeted mutation 1.2, John C Cambier
MGI accession ID: MGI:5639232
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sting1
Marker name: stimulator of interferon response cGAMP interactor 1
Chromosome: 18
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: An FRT-flanked neo cassette followed by a loxP site was inserted intron 5. A second loxP site was inserted in intron 2. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exons 3 through 5 floxed. Cre-mediated recombination removed exons 3 through 5.