SOD1-G93A Mouse Model

SOD1-G93A mice express human SOD1 with the G93A mutation under control of the cistronic human SOD1 promotor. Mutations in this gene have been linked to familial amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). The SOD1-G93A mice show a phenotype, similar to ALS in humans. Mice develop paralysis in one or more limbs within a few weeks of age. These mice are a valuable tool to study the influence of new drugs on neuromuscular disorders such as ALS.

The most important characteristics of SOD1-G93A mice are:

Early muscle weakness
Early motor deficits
Severely reduced mean survival
Oxidative stress
Neuroinflammation

Robust muscle weakness can be observed in SOD1-G93A mice as early as 15 weeks of age. Significantly increased oxidative stress levels as measured by lipid peroxidation as well as increased neuroinflammation as measured by labeling astrocytes with an GFAP antibody in SOD1-G93A mice can be observed at an age of 18-20 weeks (Fig.1).

Figure 1: Longitudinal grip strength measurement of SOD1-G93A mice, lipid peroxidase in the lumbar and thoracic spinal cord and astrocytosis in the ventral thalamus of SOD1-G93A mice at the age of 18-20 weeks. A: Force in gram that animals use to grip the handle during the grip strength test. Two-way ANOVA followed by Bonferroni’s post hoc test. Mean ± SEM; B: TBARS assay, mean + SEM; Two-way ANOVA followed by Bonferroni’s post hoc test. MDA: malondialdehyde; C: Quantitative analysis of astrocytosis in the ventral thalamus by GFAP immunofluorescent labeling. IR: immunoreactive area; mean + SEM; t-test; *p<0.05; **p<0.01; ***p<0.001.

QPS Neuropharmacology offers a custom-tailored study design for SOD1-G93A mice, and we are flexible to accommodate your special interests. We are also happy to advise you and propose study designs. SOD1-G93A mice show a relevant ALS phenotype at 15 weeks of age. This grants a remarkable fast processing time of your ALS study. Furthermore, non-transgenic littermates are available as control animals needed for proper study design.

We are happy to evaluate the efficacy of your compound in the SOD1-G93A mouse model! The most common readouts are: