S1P1 GFP Signaling Mouse

Also known as: S1pr1tm3.1(tTA,-Arrb2)Rlp, S1P1 Tango mouse

These S1pr1 knockin mice have a bicistronic transcription unit inserted at the C-terminus of exon 2 of the sphingosine-1-phosphate receptor 1 (S1pr1) gene. Specifically, the allele contains two fusion proteins, a tetracycline-regulated transactivator (tTA)-tobacco etch virus (TEV) protease recognition sequence (tevs) fusion protein and an Arrb2 (murine β-arrestin)-TEV protease fusion protein, separated by an internal ribosome entry site (IRES). Homozygous mice are viable and fertile. S1PR1 is a G protein-coupled receptor (GPCR) that acts as a regulator of vascular development and function in endothelial cells, and has been shown to play a role in autoimmunity and inflammation. In this strain, S1PR tethers tTA to the membrane. Ligand activation of S1PR1 results in phosphorylation of the receptor and subsequent recognition of the tevs sequence by the β-arrestin-TEV protease fusion protein, triggering the release of tTA. Free tTA is then able to enter the nucleus where it regulates transcription of genes of interest under the regulatory control of a tetracycline-responsive promoter element (TRE; tetO). The transcriptional regulation elicited by tTA is blocked by the administration of the tetracycline analog, doxycycline.

When mated to Tg(tetO-HIST1H2BJ/GFP)47Efu/J transgenic mice (Jackson Lab: Stock No. 005104), resulting S1P1 GFP signaling mice exhibit tTA-induced dox-dependent green fluorescent protein expression in cells where S1P1 signaling pathway is activated. Fluorescence is evident in thymi, spleen, lymph nodes, lungs, and heart. Learn more on PubMed.

Mice can be obtained from Jackson Labs.

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Proia, Richard

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Last Reviewed August 2023