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TDP-43 Transgenic Mouse Models

The TAR DNA binding protein (TDP-43) is encoded by the TARDBP gene and 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).

TAR6/6 mice express human TDP-43 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.

The most important characteristics of TAR6/6 mice are:
  • Increased TDP-43 levels and aggregations
  • Motor deficits
  • Learning deficits
  • Neuroinflammation
  • Neuron loss

Figure 1: Quantitative human TDP-43 expression in the hippocampus and spinal cord of TAR6/6, TAR6 and ntg mice at the age of 6, 14 and 24 weeks. 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: Neurofilament light chain (NF-L) levels in the plasma of TDP-43 transgenic TAR6/6 mice. NF-L levels in the plasma of TAR6/6 mice (TDP-43) at the age of 9 weeks as model of ALS; TAR6/6: n = 6, ntg: n = 4; unpaired t-test. Mean + SEM. ***p<0.001.


Figure 3: Latency to fall from the RotaRod of TAR6/6 transgenic mice at the age of 6 and 14 to 17 weeks compared to age-matched 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.

Additionally, Scantox offers research with the TAR4/4 mice as describes by Wils and colleagues (PNAS USA.2010Feb23;107(8):3858-63.). TAR4/4 mice present a stronger and earlier phenotype compared to TAR6/6 mice.

Scantox offers a custom-tailored study design for TAR6/6 and TAR4/4 mice, and we are flexible to accommodate your special interest. We are also happy to advice you and propose study designs. TAR4/4 and TAR6/ mice show a relevant ALS (PD) at early 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 TAR4/4 or TAR6/6 mouse model! The most common readouts are:

Looking for something else? Please contact us!

You might be also interested in these related models:

As with many other in vivo models we are also ready to provide samples (brain tissue, CSF etc.) from these animals for analyses in your laboratory.

We are happy to receive your inquiry.