Absence of Neuromuscular Dysfunction in Mice with Gut Epithelium-Restricted Expression of ALS Mutation hSOD1G93A

Authors
Dong, Li, Li, Xuejun, Li, Ang, Yi, Jianxun, Vockery, Yanan, Chang, Yan, Pan, Zui, Brotto, Marco, Zhou, Jingsong


Lab
* Author to whom correspondence should be addressed.; Author to whom correspondence should be addressed.; Primary and Hospital Care

Journal
Biomolecules

Abstract
Amyotrophic Lateral Sclerosis (ALS) is a devastating neuromuscular disorder characterized by the progressive loss of motor neurons and skeletal muscle, ultimately leading to respiratory failure and death, typically within 3–5 years following diagnosis. While the death of motor neurons is the pathological hallmark, ALS is increasingly recognized as a systemic disorder involving non-motor systems. Gastrointestinal dysfunction has been widely observed in both ALS patients and animal models. However, because gut abnormalities and neuromuscular degeneration are intertwined during ALS disease progression, it remains unclear whether these gut abnormalities are merely a consequence of neuromuscular degeneration or whether they play a crucial role in initiating it. In this study, we investigated whether an ALS-associated mutation expressed exclusively in the gut can directly affect neuromuscular function. We generated a novel transgenic mouse model, Gut-hG93A, which overexpresses the human ALS mutation hSOD1G93A specifically in the epithelial cells of the intestine at a level comparable to the endogenous mouse SOD1. We found that the specific overexpression of hSOD1G93A in gut epithelial cells did not cause abnormalities in the structure of the tight junctions or in gut permeability. Furthermore, there were no significant differences between Gut-hG93A and control mice regarding lifespan, body weight, or neuromuscular activities, including grip strength, daily travel distance and in vivo muscle contractility. These findings suggest that the ALS-associated hSOD1G93A mutation, when expressed solely in the gut epithelium, is not sufficient to initiate neuromuscular degeneration of systemic ALS-like pathology.

Keywords/Topics
mice; respiratory failure; gastrointestinal dysfunction; animal models; neuromuscular degeneration; grip strength; absence; neuromuscular dysfunction; gut epithelium-restricted expression; als mutation hsod1g93a

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.mdpi.com/2218-273X/16/2/253

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