B6J.B6N-Sting1^em1Jmin/J

Stock number: 033543
Product name: STING N153S

Strain synonyms: formerly Tmem173^em1Jmin

Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

STING N153S knock-in mice carry an N153S (asparagine to serine) substitution in the Sting1 (stimulator of interferon response cGAMP interactor 1) gene. Heterozygous mice develop progressive lung inflammation, hypercytokinemia, T cell cytopenia, skin ulcerations, and die by one year of age. These mice may be useful for studying (STING)-associated vasculopathy with onset in infancy (SAVI).

A floxed-Stop STING N153S conditional allele is also available (Stock No. 039266).

Detailed description

The STING N153S mutation replaces asparagine with serine, and is orthologous to the N154S mutation in the human Sting1 (stimulator of interferon response cGAMP interactor 1) gene. STING N154S is associated with (STING)-associated vasculopathy with onset in infancy (SAVI). STING (MYPS) acts as a facilitator of innate immune signaling through the detection of virus- and host-induced cyclic-GMP-AMP (cGAMP). STING also detects cytosolic bacterial pathogens and their cyclic dinucleotide metabolites. The STING N153S mutation results in embryonic lethality in the homozygous state. Mice heterozygous for the mutation develop progressive perivascular inflammation with immune cell infiltration in the lung by 4 weeks of age and usually die by one year. Pregnant females can develop severe respiratory distress during late pregnancy and may not survive labor. In addition, all STING N153S mice exhibit splenomegaly, T cell cytopenia, myeloid cell expansion, increased levels of multiple cytokines and chemokines, and hypercytokinemia. A small subset of these animals can spontaneously develop dermatitis or ulcerative skin lesions. The donating investigator indicates that mice do not develop lymph nodes or Peyer's patches. In certain mouse facilities (eg. containing Helicobacter), mice develop colitis, but do not develop colitis under SPF conditions. These mice may be useful for studying (STING)-associated vasculopathy with onset in infancy (SAVI) and innate immune response to pathogens.

A floxed-Stop STING N153S conditional allele is also available (Stock No. 039266).

Development

CRISPR/cas9 endonuclease-mediated genome editing was used to insert two nucleotide missense mutations in exon 5 of the Sting1 (stimulator of interferon response cGAMP interactor 1) gene. The mutation results in an amino acid substitution at position 153 altering asparagine to serine (N153S; AAT to TCT). Single guide RNA and Cas9 endonuclease were introduced into C57BL/6N-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to wild-type mice for germline transmission. The colony was backcrossed to C57BL/6J for at least 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Allele

Symbol: Sting1^em1Jmin
Name: endonuclease-mediated mutation 1, Jonathan Miner
MGI accession ID: MGI:6287305
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: STING N153S; SAVI
Marker symbol: Sting1
Marker name: stimulator of interferon response cGAMP interactor 1
Marker synonyms: 2610307O08Rik; ERIS; hMITA; hSTING; MITA; MPYS; NET23; RGD1562552; rSTING; SAVI; Sting; STING-beta; Tmem173
Chromosome: 18
Strain of origin: C57BL/6N
Molecular note: CRISPR/cas9 endonuclease-mediated genome editing is used to insert two nucleotide missense mutations in exon 5 of the gene. The mutation results in an amino acid substitution at position 153 altering asparagine to serine (N153S; AAT to TCT). The STING N153S mutation is analogous to the N154S mutation in human TMEM173. N154S is associated with (STING)-associated vasculopathy with onset in infancy (SAVI).