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Updated: Sep 30, 2025
In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
Published on: June 15, 2018
Loss of mouse Stmn2 function causes motor neuropathy
Irune Guerra San Juan1, Leslie A Nash2, Kevin S Smith2
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands; Human Genetics, Amsterdam University Medical Center, 1081 HV Amsterdam, the Netherlands.
Loss of the STMN2 gene, regulated by TDP43, causes motor neuron degeneration and impaired motor behavior in mice. This suggests TDP43 dysfunction contributes to amyotrophic lateral sclerosis (ALS).
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) involves motor neuron degeneration linked to TDP43 protein dysfunction.
- The precise contribution of TDP43 loss-of-function to motor system deficits is not fully understood.
Purpose of the Study:
- To investigate the role of the STMN2 gene, regulated by TDP43, in maintaining motor system function.
- To determine if disrupting STMN2 function contributes to motor neuron degeneration.
Main Methods:
- Gene editing was used to create mice with loss-of-function mutations in the Stmn2 gene.
- Phenotypic analysis included neuromuscular junction integrity, motor behavior, and neuronal microtubule dynamics.
- Rescue experiments involved BAC transgenesis to introduce human STMN2.
Main Results:
- Stmn2 loss-of-function mice exhibited neuromuscular junction denervation and fragmentation.
- These mice showed muscle atrophy and impaired motor behavior.
- Alterations in neuronal microtubule dynamics were observed in the spinal cord.
Conclusions:
- Disrupting the STMN2 gene, a target of TDP43, is sufficient to cause significant motor dysfunction.
- These findings support the hypothesis that TDP43 dysfunction contributes to the motor deficits seen in ALS.
