SD-hSCN10A(Nav1.8) Rat

Catalog Number: CR006

Strain Name: SD-Scn10aem1(hSCN10A)/Cya

Genetic Background: Sprague-Dawley

Reproduction: Homozygote x Homozygote

 

Strain Description

The SCN10A gene, which encodes the sodium channel Na(v)1.8, is a susceptibility factor for cardiac conduction block and severe ventricular arrhythmias. Genetic variations in ion channel genes are associated with hereditary arrhythmias, such as Long QT Syndrome, Short QT Syndrome, Brugada Syndrome (BrS), and conduction abnormalities. These variations are also linked to sudden unexplained death (SUD) in young adults and children. Several studies have identified common variants of SCN10A as potential regulators of human PR and QRS durations, with SCN10A being a major susceptibility gene for BrS [1-2]. The Nav1.8 protein is expressed in small-diameter sensory neurons of the trigeminal ganglion and dorsal root ganglion (DRG), as well as in some medium- and large-diameter neurons and in layers I and II of the spinal dorsal horn [3]. The SCN10A/Nav1.8 voltage-gated sodium channel is crucial in pain management. Studies have shown that Nav1.8 channel inhibitors have the potential to become a new class of effective analgesics suitable for multimodal pain treatment in postoperative patients. Additionally, the low expression of SCN10A in the brain suggests a lower likelihood of adverse effects, including dependency and abuse, within the central nervous system [4]. In early 2025, the FDA approved Suzetrigine, a Nav1.8 inhibitor developed by Vertex Pharmaceuticals, marking a breakthrough in the pain management field previously dominated by opioid drugs. As the first non-opioid acute pain medication in two decades, the success of Suzetrigine is a significant milestone.

SD-hSCN10A (Nav1.8) rats are a Scn10a humanized model created by inserting the human SCN10A gene's coding sequence (CDS) and 3'UTR into the rat Scn10a gene. This model can be used for mechanistic studies of acute pain and diabetic peripheral neuropathic pain and the development, screening, and evaluation of analgesic drugs in preclinical research.

Strain Strategy


Figure 1. Gene editing strategy of SD-hSCN10A(Nav1.8) rat. The partial coding sequence of exon 2 of rat Scn10a was replaced with the Kozak-Human SCN10A CDS-3'UTR of Human SCN10A-WPRE-BGH pA cassette.

 

Application

  • Mechanisms of acute pain, diabetic peripheral neuropathic pain, and postoperative pain;
  • Preclinical studies on the development, screening, and evaluation of analgesics targeting the Nav1.8 channel.

 

References
[1]Gando I, Williams N, Fishman GI, Sampson BA, Tang Y, Coetzee WA. Functional characterization of SCN10A variants in several cases of sudden unexplained death. Forensic Sci Int. 2019 Aug;301:289-298.
[2]Hu D, Barajas-Martínez H, Pfeiffer R, Dezi F, Pfeiffer J, Buch T, Betzenhauser MJ, Belardinelli L, Kahlig KM, Rajamani S, DeAntonio HJ, Myerburg RJ, Ito H, Deshmukh P, Marieb M, Nam GB, Bhatia A, Hasdemir C, Haïssaguerre M, Veltmann C, Schimpf R, Borggrefe M, Viskin S, Antzelevitch C. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol. 2014 Jul 8;64(1):66-79.
[3]Xue Y, Chidiac C, Herault Y, Gaveriaux-Ruff C. Pain behavior in SCN9A (Nav1.7) and SCN10A (Nav1.8) mutant rodent models. Neurosci Lett. 2021 May 14;753:135844.
[4]Kaye AD, Everett ES, Lehuquet AM, Mason JW, Maitski R, Plessala MJ, Barrie S, Baptiste CJ, Mychaskiw G 2nd, Ahmadzadeh S, Shekoohi S, Varrassi G. Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review. Curr Pain Headache Rep. 2024 Nov;28(11):1135-1143.