Expression of pathogenic SCN9A mutations in the zebrafish: A model to study small fiber neuropathy.

Expression of pathogenic SCN9A mutations in the zebrafish: A model to study small fiber neuropathy.
Exp Neurol. 2018 Oct 11;:
Authors: Eijkenboom I, Sopacua M, Otten ABC, Gerrits MM, Hoeijmakers JGJ, Waxman SG, Lombardi R, Lauria G, Merkies ISJ, Smeets HJM, Faber CG, Vanoevelen JM, PROPANE Study Group
Abstract
Small fiber neuropathy (SFN) patients experience a spectrum of sensory abnormalities, including attenuated responses to non-noxious temperatures in combination with a decreased density of the small-nerve fibers. Gain-of-function mutations in the voltage-gated sodium channels SCN9A, SCN10A and SCN11A have been identified as an underlying genetic cause in a subpopulation of patients with SFN. Based on clinical-diagnostic tests for SFN, we have set up a panel of two read-outs reflecting SFN in zebrafish, being nerve density and behavioral responses. Nerve density was studied using a transgenic line in which the sensory neurons are GFP-labelled. For the behavioral experiments, a temperature-controlled water compartment was developed. This device allowed quantification of the behavioral response to temperature changes. By using these read-outs we demonstrated that zebrafish embryos transiently overexpressing the pathogenic human SCN9A p.(I228M) or p.(G856D) mutations both have a significantly decreased density of the small-nerve fibers. Additionally, larvae overexpressing the p.(I228M) mutation displayed a significant increase in ac...

Source: Experimental Neurology - October 11, 2018 Category: Neurology Authors: Eijkenboom I, Sopacua M, Otten ABC, Gerrits MM, Hoeijmakers JGJ, Waxman SG, Lombardi R, Lauria G, Merkies ISJ, Smeets HJM, Faber CG, Vanoevelen JM, PROPANE Study Group Tags: Exp Neurol Source Type: research