TAR DNA binding protein (TARDBP or TDP-43) is shown to play a crucial role in a growing set of neurodegenerative diseases. While strongly related to sporadic and familial forms of Amyotrophic Lateral Sclerosis (ALS), intraneuronal TDP-43 accumulation and aggregation is also related to Frontotemporal Lobar Degeneration (FTLD-TDP or formerly FTLD-U).
TAR6/6 mice express human TAR DNA binding protein (TARDBP) under regulatory control of the neuron specific Thy1 promoter (Wils et al. 2010). Mice are bred on a C57BL/6 background. Homozygous mice die prematurely at about 6 months and suffer from a severe ALS like motor phenotype.
- Increased TDP-43 levels and aggregations
- Motor deficits
- Learning deficits
- Neuron loss
Figure 1: Quantitative human TDP-43 expression in the hippocampus and spinal cord of 6, 14 and 24 week old TAR6/6, TAR6 and ntg mice. A: Densitometric analysis of human TDP-43 levels normalized to tubulin levels of hippocampal (A) and spinal cord (B) homogenates from TAR6/6, TAR6 and ntg mice at the age of 6, 14 and 24 weeks. Homogenates were separated by SDS-PAGE and probed with the indicated antibodies. One representative example of 3 is shown. Two-way ANOVA with Bonferroni‘s post hoc test. *significances between genotypes, #significances between age groups. *p<0.05, **p<0.01, ***p<0.001.
Figure 2: Latency to fall from the Rota Rod in 6 and 14 to 17 week old TAR6/6 transgenic mice compared to non-transgenic littermates (ntg). A: tg n = 5; ntg n = 7; B: tg n = 11-3; ntg n = 16-5. Unpaired t-test or Mann Whitney test depending on normal distribution. Mean ± SEM. *p<0.05; ***p<0.001.
QPS Neuropharmacology offers custom tailored study design for this model 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.
We would be happy to test your compounds in this mouse model!
The most common readouts are:
- Motor behavior (Rota Rod, Beam Walk, Wire Hanging, Nest Building)
- Memory (CFC)
- TARDBP expression
- Neuronal loss
Looking for something else? Please contact us!
You might be also interested in these related models:
- SOD1-G93A high copy number
- SOD1-G93A low copy number
As with all other in vivo models we are also ready to provide samples (brain tissue, CSF etc.) from these animals for analyses in your laboratory.