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We use both the original rNLS8 (or ΔNLS) mouse model (in-licensed by Biospective), as well as a less aggressive version implemented by Biospective:
- Original mouse model ("Off Dox"): rapid progressing (weeks)
- Biospective mouse model ("Low Dox"): slower progressing (months)
Key features of this mouse model include:
- Nuclear-to-cytoplasmic TDP-43 mislocalization
- Phosphorylated TDP-43 aggregates
- Neurodegeneration & muscle atrophy
- Brain, spinal cord, and neuromuscular junction pathology
- Motor deficits
Briefly, mice are on a doxycycline (Dox) diet during breeding and the initial aging period (5 to 12 weeks-of-age). In the standard model, the mice are changed from a Dox diet to a standard diet ("Off Dox" model) to allow for human TDP-43 expression. In the Biospective-modified model, the mice are switched from the Dox diet to a standard diet for a short period and then maintained on a lower Dox dose diet ("Low Dox" model).
A unique feature of this model is the ability to achieve functional and pathologic recovery by placing the mice back on a doxycycline diet to halt TDP-43 expression.
Low and high magnification views of human pan-TDP-43 pathology in the brain. Note the strong staining of cytoplasmic aggregates and lack of nuclear staining.
Please note that we provide a link to our ALS and other CNS disease models on the last page of this presentation.