|
| Status |
Public on Jan 03, 2016 |
| Title |
Differential gene regulation downstream of murine Tmem173 variants |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We report positional cloning and characterization of a novel Sting allele that fails to activate IFN production in the wild-derived mice of MOLF/Ei strain in response to HSV (Herpes Simplex Virus) and Listeria monocytogenes both in vitro and in vivo. We show that previously uncharacterized mutations in the N-terminal of STING are responsible for low levels of IFN due to failure of MOLF STING to respond to cytosolic STING agonists such as 2’3’cGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) or poly(deoxyadenylic-deoxythymidylic) acid (dAdT). Using Next-Generation Sequencing (NGS) for the analysis of DNA-responses in congenic C57BL6.StingMOLF/MOLF (MOLF STING) mouse macrophages, we show that these mutations in MOLF/Ei discriminate in responses between different STING agonists. Macrophages from C57BL6.StingB6/B6¬ (B6 STING), or B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control.
|
| |
|
| Overall design |
To examine differential gene regulation downstream of murine Tmem173 (STING) allelic variants. We stimulated macrophages from B6 mice congenic for MOLF STING; macrophages from B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control.
One replicate of RNA-seq reads after each stimulation provided. Conditions are peritoneal macrophages from B6 congenic mice expressing: B6 STING, MOLF STING, or STING KO stimulated with 2’3’cGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), poly(deoxyadenylic-deoxythymidylic) acid (dAdT), or no treatment. This constitutes a total of 12 reads analyzed in this data set.
|
| |
|
| Contributor(s) |
Poltorak A, Surpris G |
| Citation(s) |
26685207 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI056234 |
Genetic analysis of inflammatory responses in wild-derived mice: Genetic Dissection of Lipopolysaccharide Response: Hyper-Responsiveness to TLR Agonists in Wild Derived Mice |
TUFTS UNIVERSITY BOSTON |
Poltorak |
| R21 AI119833 |
Activation of STING-mediated pathway(s) in T cells |
TUFTS UNIVERSITY BOSTON |
Poltorak |
|
| Submission date |
Apr 21, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Alexander Poltorak |
| Phone |
6176363596
|
| Organization name |
Tufts University
|
| Street address |
150 Harrison avenue
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02111 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (12)
|
| GSM1664501 |
B6.MOLF-TMEM173 congenic littermate homozygous for B6 STING no stimulation |
| GSM1664502 |
B6.MOLF-TMEM173 congenic littermate homozygous for B6 STING 4h 2'3' cGAMP |
| GSM1664503 |
B6.MOLF-TMEM173 congenic littermate homozygous for B6 STING 4h dAdT |
| GSM1664504 |
B6.MOLF-TMEM173 congenic littermate homozygous for B6 STING DMXAA |
| GSM1664505 |
B6.MOLF-TMEM173 congenic littermate homozygous for MOLF STING no stimulation |
| GSM1664506 |
B6.MOLF-TMEM173 congenic littermate homozygous for MOLF STING 4h 2'3' cGAMP |
| GSM1664507 |
B6.MOLF-TMEM173 congenic littermate homozygous for MOLF STING 4h dAdT |
| GSM1664508 |
B6.MOLF-TMEM173 congenic littermate homozygous for MOLF STING DMXAA |
| GSM1664509 |
STING KO no stimulation |
| GSM1664510 |
STING KO 4h 2'3' cGAMP |
| GSM1664511 |
STING KO 4h dAdT |
| GSM1664512 |
STING KO 4h DMXAA |
|
| Relations |
| BioProject |
PRJNA281931 |
| SRA |
SRP057562 |
Less...
More...