scholarly journals Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis

2014 ◽  
Vol 57 (7) ◽  
pp. 2942-2952 ◽  
Author(s):  
Lorcan Browne ◽  
Katie Lidster ◽  
Sarah Al-Izki ◽  
Lisa Clutterbuck ◽  
Cristina Posada ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Optic Neuritis ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Characterization of a gene-trap knockout mouse model of Scn2a encoding voltage-gated sodium channel Nav1.2

2020 ◽  
Author(s):  
Muriel Eaton ◽  
Jingliang Zhang ◽  
Zhixiong Ma ◽  
Anthony C. Park ◽  
Emma Lietzke ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sodium Channel ◽  
Knockout Mouse ◽  
Large Scale ◽  
Autism Spectrum ◽  
Gene Trap ◽  
Fecal Excretion ◽  
Loss Of Function ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

ABSTRACTRecent large-scale genomic studies have revealed SCN2A as one of the most frequently mutated gene in patients with neurodevelopmental disorders including autism spectrum disorder and intellectual disability. SCN2A encodes for voltage-gated sodium channel isoform 1.2 (Nav1.2), which is mainly expressed in the central nervous system and responsible for the propagation of neuronal action potentials. Homozygous knockout (null) of Scn2a is perinatal lethal, whereas heterozygous knockout of Scn2a results in mild behavior abnormalities. To achieve a more substantial, but not complete, reduction of Scn2a expression, we characterized a Scn2a deficient mouse model using a targeted gene trap knockout (gtKO) strategy to recapitulate loss-of-function SCN2A disorders. This model produces viable homozygous mice (Scn2agtKO/gtKO) that can survive to adulthood, with markedly low but detectable Nav1.2 expression. Although Scn2agtKO/gtKO adult mice possess normal olfactory, taste, hearing, and mechanical sensitivity, they have decreased thermal and cold tolerance. Innate behaviors are profoundly impaired including impaired nesting, marble burying, and mating. These mice also have increased food and water intake with subsequent increases in fecal excretion of more but smaller fecal boli. This novel Scn2a gene trap knockout mouse thus provides a unique model to study pathophysiology associated with Scn2a deficiency.

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