TDP-43-Induced ALS Mouse Model
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper motor neurons (MNs) in the brain and lower MNs in the spinal cord. Malfunctions of the nuclear protein TDP-43 (transactive response DNA binding protein of 43 kDa) have been described in most ALS patients. By injecting AAV9-hTDP-43 virus particles into the motor cortex M1 of 3 months old C57BL/6J mice, the ALS phenotype and neuronal pathology can be mimicked in vivo.
The most important characteristics of AAV9-hTDP-43 mice are:
- High hTDP-43 mRNA and protein expression
- Astrocytosis
- Neuronal loss/motor cortex shrinkage
- Clasping
Figure 1: Human TDP-43 mRNA and protein expression levels in the motor cortex of AAV9-hTDP-43-injected mice relative to controls. A: X-fold change in RNA expression assessed with ∆∆C(t) method vs. the house keeping gene HPRT. B: Human TDP-43 immunoreactive area in percent. Two-way ANOVA followed by Bonferroni’s multiple comparisons test. Mean ± SEM (n = 8) **p <0.01, ***p <0.001.
Figure 2: Longitudinal evaluation of the clasping score. Clasping score (3 = best score, 1 = worst score) of AAV9-TDP-43 and AAV9-empty-injected mice. n = 8-24 per group. Mean ± SEM Mixed-effects analysis followed by Bonferroni’s post hoc test; *p <0.05, ***p <0.001.
Scantox offers a custom-tailored study design for the AAV9-TDP-43 mouse model, and we are flexible to accommodate to your special interest. We are also happy to advise you and propose study designs. The AAV9-TDP-43 mouse model shows a relevant ALS pathology shortly after treatment. This grants a remarkable fast processing time of your ALS study. Furthermore, AAV9-empty vector-injected mice can serve as control needed for proper study design.
We are happy to evaluate the efficacy of your compound in the AAV9-TDP-43 mouse model! The most common readouts are:
- TDP-43 expression
- Clasping
