Related Experiment Video
Updated: Sep 11, 2025
06:49
A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS
Published on: October 6, 2015
19.9K
A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies
Cyril Jones Jagaraj1, Prachi Mehta1, Julie Hunter1
1Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, MND Research Centre, Macquarie University, 75 Talavera Road, Sydney, NSW, 2109, Australia.
Neuromolecular Medicine
|August 18, 2025
Summary
Modifying doxycycline levels in the TDP-43 rNLS8 mouse model slows Amyotrophic Lateral Sclerosis (ALS) progression. This creates a valuable tool for studying ALS early mechanisms and preclinical research.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration.
- TDP-43 pathology is a hallmark of nearly all ALS cases.
- The TDP-43 rNLS8 mouse model replicates key ALS features but has rapid progression.
Purpose of the Study:
- To investigate if low doxycycline concentrations can slow disease progression in the TDP-43 rNLS8 mouse model.
- To determine if this modified model is suitable for extended preclinical studies and early disease mechanism research.
Main Methods:
- The TDP-43 rNLS8 mouse model was used, with disease induced by doxycycline withdrawal.
- Low doxycycline concentrations (10-20 mg/kg) were administered to assess effects on disease progression.
- Disease progression was evaluated using rotarod performance, grip strength, neurological scores, and survival rates.
Main Results:
- Low doxycycline significantly reduced hTDP-43 ΔNLS expression.
- Disease onset was delayed by four weeks, and progression extended from six to 15 weeks.
- Survival increased threefold, while end-stage neuroinflammation and motor neuron loss remained similar to the rapid-progression model.
Conclusions:
- Maintaining low doxycycline concentrations in the TDP-43 rNLS8 mouse model effectively slows disease progression.
- This modified model offers a robust platform for preclinical ALS research and studying early disease mechanisms.
