Amyotrophic Lateral Sclerosis – TDP-43 Transgenic Mouse Model
Target the pathological hallmark of Frontotemporal Dementia (FTD)Â and almost all Amyotrophic lateral sclerosis (ALS) patients using the TDP-43 Transgenic Mouse Model
TDP-43 Transgenic Mouse Model Key Characteristics
TAR DNA binding protein (TDP-43) encoded by the TARDBP gene, is a major protein involved in the pathogenesis of Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Currently, several ALS mouse models that mimic the progressive loss of motoneurons in the motor cortex, brain stem, and spinal cord are available to test the efficacy of novel ALS therapies. Transgenic TDP-43 mouse models overexpress the mutant form of human TDP-43, leading to motoneuron degeneration and paralysis.Â
As part of its specialized neurology contract research services, InnoSer performs efficacy studies using transgenic TDP-43 mouse models, including the TDP-43(WT) and TDP-43(Q331K) mouse models of ALS. Available functional readouts in the TDP-43 mouse models include motor function testing, as well as sciatic nerve conduction electrophysiology (nerve conduction velocity [NCV], and compound muscle action potential [CMAP]).Â
✓ Available with and without disease-associated mutations.
✓ Abnormal accumulation of TDP-43.
✓ Motor deficits.
✓ Neuroinflammation.Â
✓  Neurodegeneration.
As part of InnoSer’s neurology ALS mouse model portfolio, we also offer efficacy studies in mouse models with TDP-43 pathology, including seeding TDP-43 mouse models using recombinant and/or patient-derived seeds, as well as a SOD1-G93A transgenic ALS mouse model. However, as each model is unique, modelling distinct pathophysiological of ALS, we recommend you discuss the most appropriate model with our neurology study directors.Â
InnoSer’s neurology expert team possesses relevant experience in working with multiple therapy types, including small molecules, peptides, enzymes, oligonucleotides, gene therapy (viral vectors, e.g., AAVs), and immunotherapies (antibody/vaccine immunotherapies).Â
Your ALS Research Starts Here.
View study timelines, recommended readouts, and example data featuring behavioral across different ALS mouse models.
TDP-43 Transgenic Mouse Model Sample Data
TDP-43Q331K mice show reduced compound muscle action potential (CMAP) in the nerve conduction test
TDP43Q331K mice show reduced neuromuscular function. Reduction of compound muscle action potential (CMAP) amplitude was seen in TDP-43 mice, reflecting loss of functional motor axons as observed in ALS patients. Data from multiple batches were normalized to the mean of the respective WT group.Â
TDP-43Q331K mice show elevated plasma neurofilament light chain (NfL) protein concentrations
Neurofilament light chain (NfL) levels in the plasma of human TDP-43Q331K transgenic mice. Compared to WT littermates, TDP-43 mice show significantly higher concentrations of plasma NfL at 7 months (the first measured timepoint) and 9 months of age. Increasing NfL in blood (and CSF) is a marker of neuronal injury, confirming the extensive neurodegenerative phenotype observed in ALS mice.Â
4-month-old female hemizygous Prp-TDP-43-Q331K (JAX #017933) mice show reduced activity (PhenoTyper).
Spontaneous behaviour relating to the motor function of mice in the automated home-cage (PhenoTyper) is tracked at high resolution and analysed by AHCODA. Highly discriminative parameters are produced, detecting changes in domains of motor function, circadian rhythm and others.
4-month-old female hemizygous Prp-TDP-43-Q331K (JAX #017933) mice show reduced muscle function (Weights lifting test).
The weight lifting test assesses muscle endurance in rodents. Mice are presented with objects of increasing weight. The readout of this test is the maximum weight that mouse can hold for 5 seconds.
4-month-old female hemizygous Prp-TDP-43-Q331K (JAX #017933) mice show motor deficits (Rotarod).
The Rotarod is the golden standard of assessing motor performance and learning in mice. Mice are placed on a rotating rod, with increasing rotating speed. Motor performance is measured by the maximal RPM (rounds per minute) at which mice are able to keep up with the rotating rod. Motor learning can be assessed by training mice on the rod for several trials.  Â
6-month-old female hemizygous Prp-TDP43-Q331K (JAX #017933) tested in the CatWalkâ„¢ Gait Analysis show abnormal walking patterns (Stride length).
The CatWalk™ gait analysis system enables quantification of a wide range of parameters related to footprint and gait in animals. Stride length (cm) refers to the distance between successive placements of the same paw. ​
6-month-old female hemizygous Prp-TDP43-Q331K (JAX #017933) tested in the CatWalkâ„¢ Gait Analysis show abnormal walking patterns (Body speed).
The CatWalk™ gait analysis system enables quantification of a wide range of parameters related to footprint and gait in animals. Body speed (cm/s) refers to the body movement speed between two consecutive steps of the same paw.​
TDP-43 Transgenic Mouse Models Readouts
Biological Readouts
Test the efficacy of your treatments with the following biological readouts:Â
 Â
- EMG recording (Compound muscle action potential [CMAP])Â Â
- MSD (e.g. cytokines in brain/spinal cord, plasma NF-L)Â
- Immunohistochemistry (TDP-43 accumulation, neuroinflammation, neurodegeneration)Â
- Immunofluorescence and FISH
The People Behind Your Research
Thomas Vogels, PhD, In Vivo Neurology Study Director
Leads an expert team of scientists with vast experience in our Neurology models to help you choose the right model and guide your optimal study design. We provide the solution to accelerating your drug development.
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