TDP-43 transgenic Mouse Model
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 followed by 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 RotaRod in 6 and 14 to 17 weeks 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 Austria 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 Austria 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 (RotaRod, Beam Walk, Wire Hanging, Nest Building)
- Memory (CFC)
- TARDBP expression
- Neuronal loss
Looking for something else? Please contact us!
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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.
We are happy to receive your inquiry.
Kovacs GG, Milenkovic I, Wöhrer A, Höftberger R, Gelpi E, Haberler C, Hönigschnabl S, Reiner-Concin A, Heinzl H, Jungwirth S, Krampla W, Fischer P, Budka H.; Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013 Sep;126(3):365-84. doi: 10.1007/s00401-013-1157-y. Epub 2013 Jul 31.
Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S. ; TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3858-63. doi: 10.1073/pnas.0912417107. Epub 2010 Feb 3.
Janssens J, Wils H, Kleinberger G, Joris G, Cuijt I, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S.: Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol Neurobiol. 2013 Aug;48(1):22-35. doi: 10.1007/s12035-013-8427-5. Epub 2013 Mar 10.