C57BL/6J-Sting1^gt/J

Stock number: 017537
Product name: Goldenticket (Gt) , Sting^Gt
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

Goldenticket (Tmem173^gt) is an I199N missense mutant allele of the Sting gene (formerly, Tmem173). Homozygotes do not produce IFN-β in response to cyclic dinucleotides or Listeria monocytogenes infection. This strain may be useful in studies related to the detection of cytosolic pathogen DNA, innate immune responses and the exploration of the tumor microenvironment.

Detailed description

Goldenticket (Tmem173^gt) is a chemically-induced (ENU) mutant allele of the transmembrane protein 173 locus (Tmem173 or Sting) harboring a missense mutation in exon 6 - which results in an isoleucine-to-asparagine change in amino acid 199 in the C-terminal of the protein. No gene product (protein) is detected by Western blot analysis of bone marrow-derived macrophages from homozygotes. Mice homozygous for the mutation are viable and fertile. Thioglycolate-elicited peritoneal macrophages isolated from homozygotes do not produce type I interferons (IFN-β) in response to cyclic dinucleotides (c-di-GMP) or Listeria monocytogenes infection. In contrast, MPYS^-/- mice (Stock No. 025805) exhibit decreased production of IFNβ after Listeria monocytogenes infection compared to controls, and regain normal production 24 hours later.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify mice exhibiting a recessive mutation causing changes in production of type I interferons in response to Listeria monocytogenes infection. Mouse 1009 was identified in the screening, and called Gt or goldenticket. Sequencing of multiple loci revealed a single base pair change, T596A, in exon 6 of Tmem173. This missense mutation results in isoleucine-to-asparagine change in amino acid 199, in the C-terminal of the protein. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Sting1^gt
Name: goldenticket
MGI accession ID: MGI:4939597
Generation method: Chemically induced (ENU)
Marker symbol: Sting1
Marker name: stimulator of interferon response cGAMP interactor 1
Chromosome: 18
Strain of origin: C57BL/6
Molecular note: ENU mutagenesis induced a T to A transversion that results in the amino acid substitution of asparagine for isoleucine at position 199 (I199N). The absence of protein expression was confirmed by western blot analysis on macrophage extracts.