LPA1 is one of the six known receptors (LPA1-6) for lysophosphatidic acid (LPA). Constitutive Lpar1 null mutant mice have been instrumental in identifying roles for LPA-LPA1 signaling in neurobiological processes, brain development, and behavior as well as modelling human neurological diseases like neuropathic pain. Constitutive Lpar1 null mutant mice are protected from partial sciatic nerve ligation (PSNL)-induced neuropathic pain, however Lpar1 expressing cell types that are functionally responsible for mediating this protective effect are unknown. Here we report generation of a Lpar1flox/flox conditional null mutant mouse that allows cre-mediated conditional deletion combined with its use in a PSNL pain model. Lpar1flox/flox mice were crossed with cre transgenic lines driven by neural gene promoters for nestin (all neural cells), synapsin (neurons), or P0 (Schwann cells). CD11b-cre transgenic mice were also used to delete Lpar1 in microglia. PSNL-initiated pain responses were reduced following cre-mediated Lpar1 deletion with all 3 neural promoters but not the microglial promoter, supporting involvement of Schwann cells and central and/or peripheral neurons in mediating pain. Interestingly, rescue responses that were due to conditional deletion were non-identical, implicating distinct roles for Lpar1 -expressing cell types. Our results with a new Lpar1 conditional mouse mutant expand an understanding of LPA1 signaling in the PSNL model of neuropathic pain.
- Downloaded 137 times
- Download rankings, all-time:
- Site-wide: 68,713 out of 77,600
- In pharmacology and toxicology: 553 out of 676
- Year to date:
- Site-wide: 8,730 out of 77,600
- Since beginning of last month:
- Site-wide: 13,912 out of 77,600
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!