SOD1-G93A transgenic 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 Amyotrophic Lateral Sclerosis in humans. They 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 Amyotrophic Lateral Sclerosis.
Figure 1: Longitudinal grip strength measurement of SOD1 mice, lipid peroxidase in the lumbar and thoracic spinal cord and astrocytosis in the ventral thalamus of 18-20 week old SOD1 mice. A: Force that animals can use to grip the handle in grams. 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. C: Quantitative analysis of astrocytosis (GFAP) in the ventral thalamus. IR: Immunoreactive area; Mean + SEM; t-test; *p<0.05; **p<0.01; ***p<0.001.
SOD1-G93A low copy number transgenic Mouse Model
QPS Neuropharmacology also offers research services with the SOD1 low copy number mouse model. Animals develop a similar phenotype as the above described SOD1 high copy number mouse model, but disease onset is at about 6-7 months and thus extending the treatment window. Animals survive appr. 6 weeks after symptom onset.
Figure 2: Astrocytosis and activated microglia in the spinal cord of 24 to 30 week old SOD1-G93A/low mice. 24, 27 and 30 week old SOD1-G93A/low mice were evaluated for GFAP and Iba1 expression in the cervical (A), thoracic (B) and lumbar (C) ventral horn compared to ntg littermates. Two-way ANOVA with Tukey‘s and Sidak’s multiple comparison post hoc test; n = 4 per group. Mean + SEM. *p<0.05, **p<0.01, ***p<0.001. *differences between genotypes; #differences between age groups. QPS Neuropharmacology offers custom tailored study design for these models and we are flexible to accommodate to your special interest. We are also happy to advice you and propose study designs. QPS Neuropharmacology maintains its own colony directly in our research facility. Non-transgenic littermates are available as control animals needed for proper study design.
Figure 3: Neurofilament light chain (NF-L) levels in the plasma of SOD1-G93A/low mice. NF-L levels in the plasma of 24 weeks old SOD1-G93A/low expressor mice as model of amyotrophic lateral sclerosis; SOD1-G93A: n = 6, ntg: n = 6; unpaired t-test. Mean + SEM. ***p<0.001.
We would be happy to test your compounds in this mouse model!
The most common readouts are:
- SOD1 aggregates
- Oxidative Stress
- Clinical signs / Vercelli Score
- Motor deficits (RotaRod, Beam Walk, Wire Hanging, Grip Strength, Nest Building)
Looking for something else? Please contact us!